0000000000048383
AUTHOR
Heinz Kilbinger
showing 69 related works from this author
The Non-neuronal Cholinergic System
2001
An increasing body of knowledge indicates that the cholinergic system is not confined to the nervous system, but is practically ubiquitous. The present paper will address the question of the non-neuronal cholinergic system in vascular endothelial cells (EC). In tissue sections of human skin, immunohistochemical studies using confocal laser scanning microscopy showed ChAT (choline acetyltransferase) activity in the EC of dermal blood vessels. Positive ChAT immunoreactivity was also demonstrated in monolayer cultures of human umbilical vein EC (HUVEC) and a human angiosarcoma EC line (HAEND). That the synthesizing enzyme is not only present in EC, but also active was shown by measuring ChAT a…
Cholinergic and GABAergic regulation of nitric oxide synthesis in the guinea pig ileum.
1999
Nitric oxide (NO) synthesis was examined in intact longitudinal muscle-myenteric plexus preparations of the guinea pig ileum by determining the formation of [3H]citrulline during incubation with [3H]arginine. Spontaneous [3H]citrulline production after 30 min was 80–90 dpm/mg, which constituted ∼1% of the tissue radioactivity. Electrical stimulation (10 Hz) led to a threefold increase in [3H]citrulline formation. Removal of calcium from the medium or addition of N G-nitro-l-arginine strongly inhibited both spontaneous and electrically induced production of [3H]citrulline. TTX reduced the electrically induced but not spontaneous [3H]citrulline formation. The electrically induced formation o…
Modulation by Scopolamine, Acetylcholine and Choline of the Evoked Release of Acetylcholine from the Guinea Pig Myenteric Plexus: Evidence for a Musc…
1981
There is evidence that the release of acetylcholine (ACh) from the guinea pig myenteric plexus is controlled via presynaptic muscarine receptors. Muscarinic antagonists such as atropine enhance the release evoked by either electrical field stimulation, by nicotinic drugs or by high K+ concentrations (4,7,10). On the other hand, the muscarinic agonist oxotremorine inhibits the evoked release of ACh (7). A comparable feedback inhibition has been described for the release of ACh from central cholinergic nerves (for review, see Ref. 12). However, it has so far not been shown whether the physiological transmitter itself is able to depress the release of neuronal ACh. We have, therefore, studied …
Release of non-neuronal acetylcholine from the human placenta: difference to neuronal acetylcholine
2001
The synthesis and release of non-neuronal acetylcholine, a widely expressed signaling molecule, were investigated in the human placenta. This tissue is free of cholinergic neurons, i.e. a contamination of neuronal acetylcholine can be excluded. The villus showed a choline acetyltransferase (ChAT) activity of 0.65 nmol/mg protein per h and contained 500 nmol acetylcholine/g dry weight. In the absence of cholinesterase inhibitors the release of acetylcholine from isolated villus pieces amounted to 1.3 nmol/g wet weight per 10 min corresponding to a fractional release rate of 0.13% per min. The following substances did not significantly modify the release of acetylcholine: oxotremorine (1 micr…
Pre- and Postsynaptic Effects of Muscarinic Antagonists in the Isolated Guinea Pig Ileum
1986
Several compounds have been claimed to differentiate between subtypes of muscarinic receptors (2). In the experiments described in this chapter we have studied in the guinea-pig ileum whether the presynaptic muscarinic receptors of the cholinergic nerves differ from the postsynaptic muscarinic receptors of the longitudinal muscle in their affinities for several muscarinic antagonists (methylatropine; trihexyphenidyl; clozapine; DAMP). Inhibition by oxotremorine of the evoked release of acetylcholine (ACh) was used as a parameter of presynaptic activity, and the increase by oxotremorine of smooth muscle tension as a postsynaptic parameter. The affinity constants (pA2 values) of the antagonis…
Enhancement of guinea-pig intestinal peristalsis by blockade of muscarinic M1-receptors
1988
1. The effects of pirenzepine and hyoscine on the peristaltic reflex were investigated in the guinea-pig isolated small intestine. Peristalsis was induced by raising the intraluminal pressure and the volume of fluid propelled was taken as a measure of the efficiency of peristaltic activity. 2. Low concentrations of pirenzepine (0.1-1 nM) and of hyoscine (0.01 nM) significantly enhanced peristalsis, whereas larger concentrations of both drugs caused inhibition. Pirenzepine was about 6 times less potent than hyoscine in increasing peristalsis, but was about 100 times less potent in inhibiting it. 3. Neither tolazoline (1 microM) nor naloxone (0.3 microM) affected the stimulatory action of pir…
Adrenergic modulation of the release of 5-hydroxytryptamine from the vascularly perfused ileum of the guinea-pig
1988
1. Isolated segments of the guinea-pig ileum were vascularly perfused and the release of 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) into the portal venous effluent was determined by h.p.l.c. with electrochemical detection. Test substances were applied via the arterial perfusion medium. 2. Isoprenaline (0.1 microM) increased the outflow of 5-HT and 5-HIAA maximally by about 75% and this was antagonized by propranolol (0.1 microM). Forskolin (1-10 microM) increased the outflow of 5-HT by approximately 105% and that of 5-HIAA by approximately 55%. The phosphodiesterase inhibitor AH 21-132 (0.1-1 microM) increased the outflow of 5-HT and 5-HIAA by about 70%. Isoprenaline…
Increase by ?-adrenolytic drugs of acetylcholine release evoked by field stimulation of the guinea-pig ileum
1979
The release of acetylcholine evoked by field stimulation of the guinea-pig ileum (3 Hz) is increased by yohimbine and tolazoline but not affected by phentolamine. It is proposed that yohimbine and tolazoline by blocking alpha-adrenoceptors of the cholinergic nerves abolish the inhibition caused by endogenous noradrenaline, and thus facilitate the output of acetylcholine.
Muscarinic inhibition of acetylcholine release from a novel in vitro preparation of the guinea-pig trachea
1990
An isolated preparation of the guinea-pig trachea is described which allows the simultaneous measurement of acetylcholine release and smooth muscle contraction. Incubation of the epithelium-free preparation with [3H]choline resulted in the formation of [3H]acetylcholine. Electrical stimulation caused the release of [3H]acetylcholine and a contractile response. Tetrodotoxin and omission of calcium from the medium abolished both the evoked release and contractions. The muscarinic agonists oxotremorine, carbachol and pilocarpine concentration-dependently inhibited the electrically evoked acetylcholine release and contracted the tracheal smooth muscle. Pre- and postsynaptic EC50 values for a gi…
GABAergic inhibition of nitric oxide-mediated relaxation of guinea-pig ileum
1999
The effects of GABA receptor agonists were investigated on guinea-pig isolated ileum longitudinal muscle with intact myenteric plexus. Electrical field stimulation (1 Hz, 10 s) of the histamine (1 microM)-precontracted preparation caused a contraction followed by a relaxation. Relaxations were inhibited by L-N(G)-nitroarginine (L-NA; EC50 3 microM) in a concentration-dependent manner. The inhibitory action of 10 microM L-NA was blocked by 10 microM L-arginine but not by D-arginine, which indicates that the relaxation was largely mediated by endogenous nitric oxide (NO). Tetrodotoxin (1 microM) reduced the relaxation only by about 50%. GABA and the GABA(B) agonist, baclofen, inhibited the fi…
Benzimidazolones and renzapride facilitate acetylcholine release from guinea-pig myenteric plexus via 5-HT4 receptors
1995
The effects of the 5-HT4 receptor agonists BIMU 8, BIMU 1, renzapride and of the 5-HT1p receptor agonist 5-hydroxyindalpine on basal and electrically evoked outflow of tritium were studied in guinea-pig longitudinal muscle myenteric plexus preparations preincubated with [3H]choline. Muscle contractions were recorded simultaneously. BIMU 8 caused a calcium dependent and tetrodotoxin sensitive increase in basal [3H]outflow that was assumed to represent release of [3H]acetylcholine. In addition, BIMU 8 enhanced the release of [3H]acetylcholine and twitch contractions evoked by submaximal electrical stimulation. Ondansetron (1 μmol/l) did not change the effects of BIMU 8, but DAU 6285 and tropi…
Two types of receptors for 5-hydroxytryptamine on the cholinergic nerves of the guinea-pig myenteric plexus
1985
Abstract The effects of 5-hydroxytryptamine (5-HT) on spontaneous and electrically-evoked release of [3H]-acetylcholine (ACh) from guinea-pig myenteric plexus preparations preincubated with [3H]-choline have been investigated in the absence of cholinesterase inhibitors. 5-HT caused a transient increase in spontaneous release and an inhibition of the electrically-evoked release of [3H]-ACh. The 5-HT-induced contractions of the longitudinal muscle were clearly related to the increase in spontaneous release. The inhibitory effect was not due to activation of alpha-adrenoceptors since it was also observed in the presence of tolazoline and on strips from reserpine-pretreated guinea-pigs. After d…
Inhibition by oxotremorine of acetylcholine resting release from guinea pig-ileum longitudinal muscle strips
1975
1. Longitudinal muscle strips of the guinea-pig ileum were incubated in Tyrode solution containing either DFP or physostigmine as cholinesterase inhibior. After a 90 min preincubation period the acetylcholine resting release into the medium was determined. Acetylcholine was estimated by gas chromatography. 2. The resting release was 0.39 nmol/g×min irrespective of the cholinesterase inhibitor used. In the presence of hexamethonium, or after omission of external calcium, the resting release fell by 50 and 55%, respectively. 3. Oxotremorine (10−5 and 10−4 M) significantly inhibited the resting release of acetylcholine by 25 and 33%, respectively. The inhibitory effect of oxotremorine was comp…
Presynaptic nicotine receptors mediating a positive feed-back on transmitter release from the rat phrenic nerve.
1986
The effects of 1,1-dimethyl-4-phenylpiperazinium (DMPP) and of nicotine receptor antagonists on [3H]acetylcholine release from the rat phrenic nerve preincubated with [3H]choline were investigated in the absence and presence of cholinesterase inhibitors (presynaptic effects). Additionally, the effects of hexamethonium and tubocurarine on the muscle contraction of the indirectly stimulated diaphragm were examined (postsynaptic effects). DMPP (1-30 microM) increased (76-92%), whereas hexamethonium (0.001-1 mM) and tubocurarine (1-10 microM) decreased (52-60%) the release of [3H]acetylcholine following a train of 100 pulses at 5 Hz. The release caused by a longer train (750 pulses at 5 Hz) was…
Characterization of the muscarine receptors involved in the modulation of serotonin release from the vascularly perfused small intestine of guinea pi…
1989
Isolated small intestinal segments of the guinea pig were arterially perfused and the release of 5-hydroxytryptamine (5-HT) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) into the portal venous effluent measured by HPLC with electrochemical detection. Test substances were applied via the arterial perfusion medium. McN-A-343, pilocarpine and oxotremorine inhibited concentration-dependently the outflow of 5-HT and 5-HIAA. Pirenzepine (0.03-0.1 mumol/l) which can discriminate between M1 and M2-receptor subtypes antagonized completely this inhibitory effect. In the presence of 1 mumol/l tetrodotoxin (TTx), all three muscarine receptor agonists increased the outflow of 5-HT and 5-HIAA. O…
Choline inhibits acetylcholine release via presynaptic muscarine receptors
1981
The effect of exogenous choline on the outflow of 3H-acetylcholine evoked by field stimulation was studied on the myenteric plexus-longitudinal muscle preparation of the guinea pig. Choline at concentrations of 100 microM and higher depressed the evoked outflow of 3H-acetylcholine in a concentration-dependent manner. The EC50 for the inhibitory action was 300 microM. Scopolamine (10 nM) antagonized the effect of choline which indicates that the inhibition of 3H-acetylcholine outflow is mediated by muscarine receptors. The findings imply that choline at high concentrations does not improve cholinergic synaptic neurotransmission in tissues that are endowed with presynaptic muscarine receptors…
Cisplatin increases the release of 5-hydroxytryptamine (5-HT) from the isolated vascularly perfused small intestine of the guinea-pig: Involvement of…
1991
Isolated segments of the guinea-pig small intestine were vascularly perfused and the release of 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) into the portal venous effluent determined by high pressure liquid chromatography with electrochemical detection. Release of acetylcholine from isolated superfused intestinal segments was determined as outflow of [3H]radioactivity from preparations preincubated with [3H]choline. Cisplatin (3 microM) increased the outflow of 5-HT and 5-HIAA by about 90%. At 30 and 100 microM cisplatin decreased the outflow of 5-HT and its metabolite by 40%-50%. The stimulatory effect of cisplatin was consistently observed only when the bicarbonate-…
The effects of metoclopramide on acetylcholine release and on smooth muscle response in the isolated guinea-pig ileum
1982
The effects of metoclopramide on smooth muscle contraction and on release of acetylcholine were studied in the guinea-pig myenteric plexus longitudinal muscle preparation. Acetylcholine was determined either as endogenous acetylcholine, or as labelled transmitter from strips preloaded with 3H-choline. Metoclopramide caused an increase in resting tension of longitudinal muscle as well as an increase in resting output of either endogenous or labelled acetylcholine. Tetrodotoxin abolished the metoclopramide-evoked increase in transmitter release. The increase in smooth muscle tension was clearly related to the increase in resting output. The effects of metoclopramide on both longitudinal muscl…
Two types of neuronal muscarine receptors modulating acetylcholine release from guinea-pig myenteric plexus
1985
Longitudinal muscle strips of the guinea-pig ileum were incubated with [3H]choline and the effects of muscarinic agonists on smooth muscle contraction and on spontaneous and electrically-evoked outflow of tritium were studied. Muscarine and pilocarpine concentration-dependently increased both muscle contraction and spontaneous outflow of [3H]ACh, and inhibited the electrically-evoked outflow of [3H]ACh. The increase in spontaneous outflow was prevented by tetrodotoxin and scopolamine, but not by hexamethonium. Oxotremorine (1-100 microM) did not increase the spontaneous outflow of tritium. Pirenzepine in concentrations of 10 and 100 nM hardly affected the muscle contractions induced by pilo…
Release of [3H]acetylcholine from a modified rat phrenic nerve-hemidiaphragm preparation
1986
Two different preparations of the rat phrenic nerve-hemidiaphragm (whole nerve-muscle preparation, end-plate preparation) were used for studying synthesis and release of radioactive acetylcholine in the absence and presence of cholinesterase inhibitors. When the whole nerve-muscle preparation (110-180 mg) was incubated with [3H]choline, only small amounts of radioactive acetylcholine were synthesized within the tissue. Electrical nerve stimulation of the whole nerve-muscle preparation produced no increase in tritium outflow. Incubation of the end-plate preparation (16-29 mg) which was obtained after removal of most of the muscle mass led to the formation of large amounts of [3H]acetylcholin…
Applicability of the isolated perfused rat brain for studying central cholinergic mechanisms.
1974
The ACh content of the isolated perfused rat brain as well as that of the rat brain in vivo was determined by gas chromatography. After a perfusion period of 30 min the endogenous ACh content of the isolated brain was significantly higher than that of the brain in vivo. Physostigmine caused a rise in the ACh concentration of both the isolated brain and the brain in vivo. Oxotremorine produced an increase in the ACh content in the brain in vivo, but not in the isolated brain after appropriate dosage. The concentration of the drugs in the perfusion medium of the isolated brain was so that distinct EEG changes could be observed but spontaneous electrical activity could be maintained during the…
NK1- and NK3-receptor mediated inhibition of 5-hydroxytryptamine release from the vascularly perfused small intestine of the guinea-pig
1997
The effects of tachykinins on the spontaneous release of 5-hydroxytryptamine (5-HT) from the enterochromaffin cells into the portal circulation was investigated in vitro using the vascularly perfused isolated guinea-pig small intestine. 5-HT was determined by HPLC with electrochemical detection. Test substances were applied intraarterially. Substance P (SP) caused a concentration-dependent decrease in 5-HT outflow with an EC50 of 50 pmol/l. Similarly, the selective NK1 receptor agonist SP methyl ester (1 nmol/l) significantly inhibited 5-HT outflow (to 51 +/- 3%). When tetrodotoxin (1 mumol/l) was added to the arterial perfusion medium, the inhibition by SP of 5-HT outflow was not affected.…
Effects of (+)-tubocurarine on [3H]acetylcholine release from the rat phrenic nerve at different stimulation frequencies and train lengths
1987
The effect of (+)-tubocurarine (TC) on the release of [3H]acetylcholine from the rat phrenic nerve-hemidiaphragm preincubated with [3H]choline was investigated at different stimulation frequencies and train lengths. At 0.5 Hz (100 pulses) TC failed to modulate the evoked acetylcholine release. A slight (30%) inhibition was observed at 1 Hz (100 pulses). Release of acetylcholine evoked at 5, 25 and 50 Hz (100 pulses) or 100 Hz (200 pulses) was markedly reduced by TC. The degree of inhibition (60%) was similar between 5 Hz and 100 Hz. A concentration of 1 mumol/l TC was a maximal effective concentration at 5 Hz whilst at all higher stimulation frequencies a 10-fold higher concentration was ne…
Pre- and Postjunctional Muscarinic Receptors in the Guinea-pig Trachea
1991
ABSTRACT The effects of M2- and Me-selective muscarinic antagonists on electrically evoked [3H]acetylcholine release and muscle contraction were compared in the isolated guinea-pig trachea. The M2-selective antagonists methoctramine and AF-DX 116 were more potent in enhancing the evoked release than in inhibiting the contractile response. As a consequence of the selective blockade of the inhibitory autoreceptors the evoked muscle contractions were enhanced by low concentrations (0.1 μmol/l) of the M2-selective antagonists. The Me-selective antagonists 4-DAMP, UH-AH 37 and pFHHSiD were more potent in reducing the contraction than in facilitating the evoked release. Surprisingly, HHSiD did no…
Proliferative effect of acetylcholine on rat trachea epithelial cells is mediated by nicotinic receptors and muscarinic receptors of the M1-subtype.
2003
Acetylcholine (ACh), synthesized in mammalian non-neuronal cells such as epithelial cells of the airways, digestive tract and skin, is involved in the regulation of basic cell functions (so-called non-neuronal cholinergic system). In the present experiments rat trachea epithelial cells have been cultured to study the proliferative effect of applied ACh by [3H]thymidine incorporation. ACh (exposure time 24 h) caused a concentration-dependent increase in cell proliferation with a doubling of the [3H]thymidine incorporation at a concentration of 0.1 microM. This effect was partly reduced by 30 microM tubocurarine and completely abolished by the additional application of 1 microM atropine. The …
Antagonist discrimination between subtypes of tachykinin receptors in the guinea-pig ileum.
1986
1. The effects of substance P and eledoisin on spontaneous and electrically-evoked release of [3H]acetylcholine, and on smooth muscle were studied in the guineapig myenteric plexus-longitudinal muscle preparation preloaded with [3H]choline. Substance P and eledoisin caused transient increases in spontaneous release of [3H]acetylcholine and in longitudinal muscle tone. Both tachykinins were equipotent in contracting the muscle, but eledoisin was more potent than substance P in eliciting [3H]acetylcholine release. The release caused by substance P was enhanced in the presence of naloxone and scopolamine which suggests that the release is modulated through opioid and muscarinic receptors. 2. S…
The effects of LSD in the guinea-pig ileum
1985
The effects of lysergic acid diethylamide (LSD) on acetylcholine release and on smooth muscle tone were studied in the myenteric plexus-longitudinal muscle preparation of the guinea pig. LSD (0.01-10 microM) depressed in a concentration-dependent manner the electrically-evoked [3H]-acetylcholine outflow from strips preincubated with [3H]-choline. The maximal effect was a 45% inhibition by 1 microM LSD. The spontaneous outflow was not affected. Metitepine competitively antagonized (pA2 8.0) the LSD-induced reduction of the evoked outflow. Tolazoline and mepyramine did not affect the inhibitory action of LSD. The contractions in response to electrical stimulation were enhanced by 34% in the p…
Acetylcholine receptors (muscarinic) in GtoPdb v.2021.3
2021
Muscarinic acetylcholine receptors (mAChRs) (nomenclature as agreed by the NC-IUPHAR Subcommittee on Muscarinic Acetylcholine Receptors [50]) are activated by the endogenous agonist acetylcholine. All five (M1-M5) mAChRs are ubiquitously expressed in the human body and are therefore attractive targets for many disorders. Functionally, M1, M3, and M5 mAChRs preferentially couple to Gq/11 proteins, whilst M2 and M4 mAChRs predominantly couple to Gi/o proteins. Both agonists and antagonists of mAChRs are clinically approved drugs, including pilocarpine for the treatment of elevated intra-ocular pressure and glaucoma, and atropine for the treatment of bradycardia and poisoning by muscarinic age…
Pre- and postsynaptic effects of muscarinic agonists in the guinea-pig ileum
1980
The effects of several muscarinic agonists on smooth muscle (postsynaptic effect) and on acetylcholine release (presynaptic effect) were compared in the longitudinal muscle-myenteric plexus preparation of the guinea-pig ileum. 1. For release experiments the acetylcholine stores of the preparation were labelled with 3H-choline. Electrical field stimulation in the absence of a cholinesterase inhibitor caused an outflow of tritium that reflected release of 3H-acetylcholine. The agonists oxotremorine, arecaidinepropargylester, methylfurmethide, muscarine, carbachol, arecoline and pilocarpine inhibited the stimulation-induced outflow in a concentration-dependent manner. At the highest concentrat…
Effects of K(ATP) channel modulators on acetylcholine release from guinea-pig isolated atria and small intestine.
2002
The effects of K(ATP) channel blockers (glibenclamide, HMR 1883, HMR 1372) and openers (cromakalim, pinacidil, diazoxide) on the electrically-evoked (5 Hz) release of [(3)H]acetylcholine were studied in isolated guinea-pig atria and myenteric plexus-longitudinal muscle preparations which had been preincubated with [(3)H]choline. Atria: Cromakalim (0.3 microM and 1 microM), pinacidil (10 microM) and diazoxide (30 microM) significantly reduced the stimulation-evoked release of [(3)H]acetylcholine. The inhibition produced by cromakalim and pinacidil was prevented by 1 microM of either HMR 1883, HMR 1372 or glibenclamide. The blockers alone significantly increased the release at concentrations …
Effect of vasoactive intestinal polypeptide on the release of serotonin from the in vitro vascularly perfused small intestine of guinea pig.
1989
Isolated segments of the guinea pig small intestine were vascularly perfused and the release of endogenous serotonin (5-HT) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) into the portal vein was measured. All test substances were intraarterially perfused. Vasoactive intestinal polypeptide (VIP, 1 pmol/l-100 nmol/l) inhibited the spontaneous release of 5-HT and 5-HIAA. The maximal inhibitory effect (about 60%) was seen at 100 pmol/l. The effect of VIP on the spontaneous release of 5-HT and 5-HIAA was not changed in the presence of 1 mumol/l tetrodotoxin (TTX). Raising intraluminal pressure by 500 Pa for 5 min increased the release of 5-HT and 5-HIAA by about 25%. Raising the intralu…
Tachykinin NK(2) receptors facilitate acetylcholine release from guinea-pig isolated trachea.
2000
The release of newly synthesised [3H]acetylcholine was evoked by electrical field stimulation (5 Hz, 600 pulses) of epithelium-deprived guinea-pig trachea strips after sensory neuropeptides depletion with 3 microM capsaicin. The selective tachykinin NK(2) receptor agonist [betaAla(8)]neurokinin A-(4-10) increased in a concentration-dependent manner the electrically-induced release of [3H]acetylcholine. The facilitatory effect was antagonised by the selective non-peptide tachykinin NK(2) receptor antagonist, SR 48968 (apparent pK(B) 8.9). The tachykinin NK(1) and NK(3) receptor agonists substance P methyl ester and senktide (both 10 and 100 nM), respectively, did not affect the evoked releas…
Acetylcholine receptors (muscarinic) in GtoPdb v.2021.2
2021
Muscarinic acetylcholine receptors (mAChRs) (nomenclature as agreed by the NC-IUPHAR Subcommittee on Muscarinic Acetylcholine Receptors [50]) are activated by the endogenous agonist acetylcholine. All five (M1-M5) mAChRs are ubiquitously expressed in the human body and are therefore attractive targets for many disorders. Functionally, M1, M3, and M5 mAChRs preferentially couple to Gq/11 proteins, whilst M2 and M4 mAChRs predominantly couple to Gi/o proteins. Both agonists and antagonists of mAChRs are clinically approved drugs, including pilocarpine for the treatment of elevated intra-ocular pressure and glaucoma, and atropine for the treatment of bradycardia and poisoning by muscarinic age…
Nitric oxide-sensitive guanylyl cyclase inhibits acetylcholine release and excitatory motor transmission in the guinea-pig ileum
1997
Abstract This study examined the mechanism through which nitric oxide inhibits the release of acetylcholine and excitatory motor neurotransmission in the guinea-pig ileum. The selective inhibitor of nitric oxide-sensitive guanylyl cyclase, 1 H -[1,2,4]oxadiazolo[4,3- a ]quinoxalin-1-one (ODQ), concentration-dependently enhanced both basal release (−log EC 50 : 6.8) and electrically (10 Hz) -evoked release (−log EC 50 : 6.0) of [ 3 H]acetylcholine from longitudinal muscle-myenteric plexus preparations preincubated with [ 3 H]choline. The increase by ODQ of basal release appeared to be exocytotic since it was prevented by tetrodotoxin (300 nM) and absence of calcium from the superfusion mediu…
Effects of cromakalim on acetylcholine release and smooth muscle contraction in guinea-pig small intestine
1989
The effects of the potassium channel opener cromakalim on smooth muscle contraction and 3H-acetyl-choline release were studied simultaneously in guinea-pig longitudinal muscle myenteric plexus preparations which had been preincubated with 3H-choline. Cromakalim (10 mumol/l) inhibited more markedly the smooth muscle contractions caused by the release of endogenous acetylcholine (via electrical stimulation or via activation of nicotine- and 5-HT3-receptors) than contractions induced by pilocarpine. Cromakalim (10 mumol/l) did not affect the release of 3H-acetylcholine evoked by electrical stimulation or by stimulation of nicotine- and 5-HT3-receptors. In contrast, the release of 3H-acetylchol…
The variation of acetylcholine release from myenteric neurones with stimulation frequency and train length. Role of presynaptic muscarine receptors.
1983
1. The effects of scopolamine on the release of 3H-acetylcholine (ACh) from the guinea-pig myenteric plexus were studied at different stimulation frequencies (0.03–10 Hz) and train lengths (1–180 pulses). Release of 3H-ACh was measured in the absence of cholinesterase inhibitors as the outflow of tritium from myenteric plexus-longitudinal muscle preparations preloaded with 3H-choline. 2. In control experiments the volley output of 3H-ACh declined with increasing train length and increasing stimulation frequency. Stimulation by one pulse produced the highest volley output. 3. Scopolamine facilitated the evoked output of 3H-ACh via blockade of presynaptic muscarine receptors. A significant in…
Absence of muscarinic modulation of vasopressin release from the isolated rat neurohypophysis
1975
1. Isolated rat neurohypophyses were incubated in Locke solution at 37°C and the vasopressin output into the medium determined by bioassay. 2. Potassium chloride 60 mM caused a 9-fold increase in the rate of vasopressin release that was abolished when calcium chloride was omitted from the Locke solution. 3. Acetylcholine 5.5×10−4 M neither alone nor in the presence of atropine 2.9×10−6 M changed the “resting” release of vasopressin. 4. Neither acetylcholine 5.5×10−4 M nor oxotremorine 10−4 and 3×10−4 M altered the vasopressin release evoked by potassium chloride 60 mM. 5. In contrast to the peripheral adrenergic nerve fibres, the secretory terminal fibres of the neurohypophysis do not appea…
Some pharmacological properties of the false cholinergic transmitter acetylpyrrolidinecholine and its precursor pyrrolidinecholine
1976
The acetylchline analogue acetylpyrrolidinecholine as well as the choline analogue pyrrolidinecholine were synthesized and the cholinergic properties of both substances were investigated on the guinea-pig ileum, rat blood pressure and frog rectus abdominis muscle. Acetylpyrrolidinecholine was 3-5 times less potent than acetylcholine on the three preparations tested. The dose-response curves to acetylpyrrolidinecholine were shifted to the right in a parallel manner by atropine and (+)-tubocurarine. The dissociation constants for atropine and (+)-tubocurarine obtained with acetylpyrrolidinecholine as agonist were not different from those obtained with acetylcholine. This indicates that acetyl…
The non-neuronal cholinergic system in humans: expression, function and pathophysiology.
2003
Acetylcholine, a prime example of a neurotransmitter, has been detected in bacteria, algae, protozoa, and primitive plants, indicating an extremely early appearance in the evolutionary process (about 3 billion years). In humans, acetylcholine and/or the synthesizing enzyme, choline acetyltransferase (ChAT), have been found in epithelial cells (airways, alimentary tract, urogenital tract, epidermis), mesothelial (pleura, pericardium), endothelial, muscle and immune cells (mononuclear cells, granulocytes, alveolar macrophages, mast cells). The widespread expression of non-neuronal acetylcholine is accompanied by the ubiquitous presence of cholinesterase and receptors (nicotinic, muscarinic). …
Formation and release of acetylpyrrolidinecholine (N-methyl, N-acetoxyethylpyrrolidinium) as a false cholinergic transmitter in the myenteric plexus …
1977
1. Longitudinal muscle strips of the guineapig small intestine were incubated with Tyrode solution containing the choline analogue pyrrolidinecholine. At the end of the incubation the concentrations of acetylcholine and its analogue acetylpyrrolidinecholine were determined in the strips by gas chromatography. 2. After 120 min of incubation with 1 mM pyrrolidinecholine, acetylpyrrolidinecholine comprised about 15% of the total amount of acetylcholine plus acetylpyrrolidinecholine. Electrical stimulation (1 Hz) of the strips during the incubation slightly increased the proportion of acetylpyrrolidinecholine to 21%. 3. The acetylcholine content of control strips increased significantly during …
Effects of the benzodiazepine receptor agonist midazolam and antagonist flumazenil on 5-hydroxytryptamine release from guinea-pig intestine in vitro
1990
Isolated segments of the guinea-pig small intestine and the guinea-pig stomach were vascularly perfused and the release of 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid into the portal venous effluent determined by high pressure liquid chromatography with electrochemical detection. Test substances were applied intraarterially. The benzodiazepine receptor agonist, midazolam, concentration-dependently increased (by 58%, at 1 nmol/l) and decreased (by 32%, at 100 nmol/l) the release of 5-HT from small intestine preparations. Both effects were blocked by the benzodiazepine receptor antagonist flumazenil (10 nmol/l) The stimulatory effect of midazolam was also abolished in the presen…
Modulation by oxotremorine and atropine of acetylcholine release evoked by electrical stimulation of the myenteric plexus of the guinea-pig ileum
1977
1. The effects of oxotremorine and atropine on the release of acetylcholine from longitudinal muscle strips of the guinea-pig ileum stimulated at frequencies between 0.1 and 3 Hz in the presence of eserine were investigated. In control experiments the acetylcholine output per stimulus declined with increasing frequencies of stimulation. 2. Oxotremorine inhibited the release of acetylcholine in a concentration-dependent fashion. At a concentration of 10−6 M oxotremorine, the release evoked by 0.1 Hz was reduced by 54%. With increasing frequencies of stimulation the inhibitory effect of oxotremorine became smaller. 3. Atropine enhanced the output of acetylcholine evoked by electrical stimulat…
Modulation of acetylcholine release in the guinea-pig trachea by the nitric oxide donor, S-nitroso-N-acetyl-DL-penicillamine (SNAP)
2000
The effects of the nitric oxide (NO) donor S-nitroso-N-acetyl-DL-penicillamine (SNAP) and the NO synthase inhibitor L-N(G)-nitroarginine (L-NOARG) on the electrically evoked [(3)H]-acetylcholine release were studied in an epithelium-free preparation of guinea-pig trachea that had been preincubated with [(3)H]-choline. SNAP (100 and 300 microM) caused small but significant increases of the electrically evoked [(3)H]-acetylcholine release (121+/-4% and 124+/-10% of control). Resting outflow of [(3)H]-ACh was not affected by SNAP. The increase by SNAP was abolished by the specific inhibitor of soluble guanylyl cyclase, 1H-[1,2,4]oxadiazolo[4,3-alpha]quinoxalin-1-one (ODQ, 1 microM). The facili…
Prejunctional M1 and postjunctional M3 muscarinic receptors in the circular muscle of the guinea-pig ileum.
1995
The effects of subtype-selective muscarinic receptor antagonists on electrically evoked release of acetylcholine and muscle contraction were compared in circular muscle preparations of the guinea-pig ileum. Incubation of the preparation with [3H]choline resulted in the formation of [3H]acetylcholine. Electrical stimulation caused the release of [3H]acetylcholine which was abolished by tetrodotoxin and omission of calcium from the medium. 5-Hydroxytryptamine (10 microM) and the nicotinic agonist 1,1-dimethyl-4-phenyl-piperazinium (300 microM) did not change acetylcholine release. The muscarinic antagonists pirenzepine (M1 selective), AF-DX 116 (M2 selective) and hexahydrosiladifenidol (M3 se…
Increase by 5-hydroxykynuramine of spontaneous acetylcholine release from myenteric neurons: mediated by serotonin M receptors
1987
The effects of 5-hydroxykynuramine (5-OH-K) and of 3-(2-amino-5-hydroxyphenyl)-propaneamine (AHPP) on spontaneous and electrically evoked release of [3H]acetylcholine were studied in the guinea-pig myenteric plexus longitudinal muscle preparation preincubated with [3H]choline. 5-OH-K caused a concentration-dependent increase in spontaneous [3H]acetylcholine release (EC50 5.3 microM). This effect was diminished in the presence of a desensitizing concentration of 5-hydroxytryptamine (5-HT). AHPP (1-100 microM) did not affect the spontaneous outflow of [3H]acetylcholine. The electrically evoked release of [3H]acetylcholine was significantly reduced in the presence of 100 microM of either 5-OH-…
Differential effects of anandamide on acetylcholine release in the guinea-pig ileum mediated via vanilloid and non-CB1 cannabinoid receptors
2001
The effects of anandamide on [3H]-acetylcholine release and muscle contraction were studied on the myenteric plexus-longitudinal muscle preparation of the guinea-pig ileum preincubated with [3H]-choline. Anandamide increased both basal [3H]-acetylcholine release (pEC50 6.3) and muscle tone (pEC50 6.3). The concentration-response curves for anandamide were shifted to the right by 1 μM capsazepine (pKB 7.5 and 7.6), and by the combined blockade of NK1 and NK3 tachykinin receptors with the antagonists CP99994 plus SR142801 (each 0.1 μM). The CB1 and CB2 receptor antagonists, SR141716A (1 μM) and SR144528 (30 nM), did not modify the facilitatory effects of anandamide. Anandamide inhibited the e…
Release of non-neuronal acetylcholine from the isolated human placenta is mediated by organic cation transporters
2001
1. The release of acetylcholine was investigated in the human placenta villus, a useful model for the characterization of the non-neuronal cholinergic system. 2. Quinine, an inhibitor of organic cation transporters (OCT), reduced acetylcholine release in a reversible and concentration-dependent manner with an IC(50) value of 5 microM. The maximal effect, inhibition by 99%, occurred at a concentration of 300 microM. 3. Procaine (100 microM), a sodium channel blocker, and vesamicol (10 microM), an inhibitor of the vesicular acetylcholine transporter, were ineffective. 4. Corticosterone, an inhibitor of OCT subtype 1, 2 and 3 reduced acetylcholine in a concentration-dependent manner with an IC…
gamma-Aminobutyric acid and cholinergic transmission in the guinea-pig ileum.
1983
1. The effects of GABA on release of acetylcholine and on contractility of the smooth muscle were studied in the myenteric plexus-longitudinal muscle preparation of the guinea pig. Acetylcholine was determined as radiolabelled transmitter from strips preloaded with 3H-choline. 2. GABA (1–300 μM) caused an increase in resting tension of smooth muscle as well as an increase in release of acetylcholine that was considerably reduced by tetrodotoxin. The facilitation by GABA of acetylcholine release exhibited a marked tachyphylaxis. The increase in muscle tension was clearly related to the increase in acetylcholine release. Muscimol (0.1–10 μM) also enhanced the release of acetylcholine. The eff…
Acetylcholine receptors (muscarinic) (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database
2019
Muscarinic acetylcholine receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on Muscarinic Acetylcholine Receptors [45]) are GPCRs of the Class A, rhodopsin-like family where the endogenous agonist is acetylcholine. In addition to the agents listed in the table, AC-42, its structural analogues AC-260584 and 77-LH-28-1, N-desmethylclozapine, TBPB and LuAE51090 have been described as functionally selective agonists of the M1 receptor subtype via binding in a mode distinct from that utilized by non-selective agonists [243, 242, 253, 155, 154, 181, 137, 11, 230]. There are two pharmacologically characterised allosteric sites on muscarinic receptors, one defined by it binding gallami…
Temperature-dependent effects of increased intraluminal pressure on serotonin release from the vascularly perfused guinea pig ileum
1987
Isolated segments of the guinea pig ileum were vascularly perfused and the release of endogenous serotonin into the portal effluent was measured. Peristalsis was induced by raising the intraluminal hydrostatic pressure by 500 Pa for 5 min. Serotonin release increased during peristalsis induced by fluid of 37 degrees C, but decreased when the temperature of the intraluminal fluid was between 13 degrees C and 22 degrees C. In the presence of naloxone (0.3 mumol/l) raising the intraluminal pressure with fluid of 37 degrees C caused an inhibition of the serotonin release which was blocked by scopolamine (0.1 mumol/l). Naloxone did not affect the inhibition of serotonin release during peristalsi…
Characterization of prejunctional muscarinic autoreceptors in the guinea-pig trachea
1991
1. The effects of ten muscarinic antagonists on electrically evoked [3H]-acetylcholine release and muscle contraction were compared in an epithelium-free preparation of the guinea-pig trachea that had been preincubated with [3H]-choline. 2. The M3-selective antagonists UH-AH 37, 4-diphenyl-acetoxy-N-piperidine methobromide and para-fluorohexahydrosiladiphenidol were more potent in reducing the contractile response than in facilitating the evoked [3H]-acetylcholine release. Hexahydrosiladiphenidol did not discriminate between pre- and postjunctional effects. The rank order of the postjunctional potencies of the ten antagonists as well as the postjunctional pA2 values obtained for hexahydrosi…
GABA receptors are involved in the modulation of the release of 5-hydroxytryptamine from the vascularly perfused small intestine of the guinea-pig
1989
Isolated small intestinal segments of the guinea-pig were perfused arterially and the release of 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) into the portal venous effluent was determined by HPLC with electrochemical detection. Test substances were applied intraarterially. Muscimol (1 microM) time dependently first increased then decreased the release of 5-HT and 5-HIAA. The stimulatory effect was prevented by tetrodotoxin (TTx) or scopolamine, indicating that it was mediated by the release of acetylcholine. Bicuculline concentration dependently decreased (1 microM) or increased (10, 50 microM) the release of 5-HT and 5-HIAA, indicating that endogenous GABA also activ…
Differential effects of nitric oxide donors on basal and electrically evoked release of acetylcholine from guinea-pig myenteric neurones
1996
1. The effects of the nitric oxide (NO) donors, 3-morpholino-sydnonimine (SIN-1), S-nitroso-N-acetylpenicillamine (SNAP) and sodium nitroprusside on basal and electrically evoked release of [3H]-acetylcholine were studied in myenteric plexus longitudinal muscle preparations of the guinea-pig small intestine preincubated with [3H]-choline. 2. The NO donors concentration-dependently increased basal release of [3H]-acetylcholine. The increase in release was calcium-dependent and was prevented in the presence of tetrodotoxin. Superoxide dismutase (150 u ml-1) potentiated the effect of SIN-1. The selective inhibitor of soluble guanylyl cyclase, 1H-[1,2,4]oxadiazolo[4,3-alpha]quinoxalin-1-one (OD…
In vivo release of non-neuronal acetylcholine from the human skin as measured by dermal microdialysis: effect of botulinum toxin
2006
1.--Acetylcholine is synthesized in the majority of non-neuronal cells, for example in human skin. In the present experiments, the in vivo release of acetylcholine was measured by dermal microdialysis. 2.--Two microdialysis membranes were inserted intradermally at the medial shank of volunteers. Physiological saline containing 1 muM neostigmine was perfused at a constant rate of 4 microl min(-1) and the effluent was collected in six subsequent 20 min periods. Acetylcholine was measured by high-pressure liquid chromatography (HPLC) combined with bioreactors and electrochemical detection. 3.--Analysis of the effluent by HPLC showed an acetylcholine peak that disappeared, when the analytical c…
The Non-neuronal Cholinergic System
2001
Acetylcholine, one of the most exemplary neurotransmitters, has been detected in bacteria, algae, protozoa, tubellariae and primitive plants, suggesting an extremely early appearance in the evolutionary process and a wide expression in non-neuronal cells. In plants (Urtica dioica), acetylcholine is involved in the regulation of water resorption and photosynthesis. In humans, acetylcholine and/or the synthesizing enzyme, choline acetyltransferase, have been demonstrated in epithelial (airways, alimentary tract, urogenital tract, epidermis), mesothelial (pleura, pericardium), endothelial, muscle and immune cells (granulocytes, lymphocytes, macrophages, mast cells). The widespread expression o…
Spontaneous release of endogenous 5-hydroxytryptamine and 5-hydroxyindoleacetic acid from the isolated vascularly perfused ileum of the guinea-pig
1987
The spontaneous release of 5-hydroxytryptamine and its metabolite 5-hydroxyindoleacetic acid from the enterochromaffin cells of the small intestine into the portal circulation was investigated in vitro using the vascularly perfused ileum of the guinea-pig. The release of 5-hydroxytryptamine decreased by 70% in a calcium-free medium and by 35% in the presence of tetrodotoxin. Inhibition of monoamine oxidase activity by pargyline (100 microM) had no effect on the spontaneous release of 5-hydroxytryptamine although it caused a 75% reduction in the outflow of 5-hydroxyindoleacetic acid. Imipramine (1 microM), an inhibitor of neuronal uptake of 5-hydroxytryptamine, reduced the 5-hydroxyindoleace…
AF-DX 116 differentiates between prejunctional muscarine receptors located on noradrenergic and cholinergic nerves.
1989
Prejunctional affinity constants of the cardioselective muscarine receptor antagonist AF-DX 116 (11-[(2-[(diethyl-amino)methyl]-1-piperidinyl)acetyl]-5,11-dihydro-6 H-pyrido [2,3-b] [1,4] benzodiazepine-6-one) were determined for muscarine autoreceptors on cholinergic nerves of the guinea-pig ileum and for heteroreceptors on noradrenergic nerves of the rat heart and guinea-pig iris. AF-DX 116 antagonized with low affinity the muscarinic inhibition induced by arecaidine propargyl ester of the stimulation-evoked [3H]acetylcholine overflow (pA2 6.74) from the guinea-pig ileum. In contrast, AF-DX 116 was more potent in antagonizing the methacholine-induced inhibition of the stimulation-evoked […
Increased acetylcholine levels in skin biopsies of patients with atopic dermatitis.
2003
Recent experimental evidence indicates that non-neuronal acetylcholine is involved in the regulation of basic cell functions. Here we investigated the cholinergic system in the skin of healthy volunteers and patients with atopic dermatitis (AD). The synthesizing enzyme, choline-acetyltransferase (ChAT), was studied by anti-ChAT immunohistochemistry and enzyme assay. Skin biopsies taken from healthy volunteers and from AD patients were separated into the 2 mm superfical (epidermis and upper dermis) and 3 mm underlying portion (deeper dermis and subcutis). ChAT enzyme activity was detected in homogenized skin and subcutaneous fat (about 13 nmol/mg protein/h). ChAT immunoreactivity was express…
Modulation by NO of acetylcholine release in the ileum of wild-type and NOS gene knockout mice.
2002
Nitric oxide (NO) inhibits the release of acetylcholine and cholinergic contractions in the small intestine of several species, but no information is available about the mouse ileum. This study examines the effects of NO on the electrically evoked release of [3H]acetylcholine and smooth muscle contraction in myenteric plexus-longitudinal muscle preparations of wild-type mice and of neuronal NO synthase (nNOS) and endothelial NOS (eNOS) knockout mice. The NOS inhibitor N G-nitro-l-arginine (l-NNA) and the guanylyl cyclase inhibitor 1 H-[1,2,4]oxadiazolo[4,3-α]quinoxalin-1-one (ODQ) concentration dependently increased the evoked [3H]acetylcholine release and cholinergic contractions in prepa…
Presynaptic effects of scopolamine, oxotremorine, noradrenaline and morphine on [3H] acetylcholine release from the myenteric plexus at different sti…
1987
The inhibition by three modulators (oxotremorine, noradrenaline, morphine) of acetylcholine release from the myenteric plexus preincubated with [3H]choline was investigated at different stimulation frequencies and calcium concentrations. Moreover, [3H]acetylcholine release evoked by a low (0.1 Hz) or a high (10 Hz) stimulation rate was investigated at different calcium concentrations either in the absence or presence of scopolamine. A reduced calcium concentration (0.6 mmol/l) inhibited acetylcholine release more at 0.1 Hz (74% +/- 3%) than at 10 Hz (44% +/- 8%). Scopolamine enhanced the stimulated acetylcholine release at a calcium concentration of 1.8 mmol/l. At calcium concentrations hig…
Increase by NO synthase inhibitors of acetylcholine release from guinea-pig myenteric plexus
1994
The effects of nitric oxide (NO) synthase inhibitors on the electrically evoked release of [3H]acetylcholine were studied in guinea-pig myenteric plexus preparations preincubated with [3H]choline. NG-monomethyl-L-arginine (EC50 5.3 mumol l-1) and NG-nitro-L-arginine (EC50 1.3 mumol l-1) concentration-dependently increased the evoked release of [3H]acetylcholine without affecting the basal outflow. The facilitatory effect of NG-mono-methyl-L-arginine was prevented by L-arginine but not by D-arginine. The results suggest that endogenous NO inhibits the depolarisation-evoked release of acetylcholine.
Cholinergic modulation of the release of 5-hydroxytryptamine from the guinea pig ileum.
1987
Isolated segments of the guinea pig ileum were vascularly perfused and the release of 5-HT and its metabolite 5-HIAA into the portal venous effluent determined by HPLC with electrochemical detection. Test substances were applied via the arterial perfusion medium. Oxotremorine inhibited concentration-dependently the release of 5-HT and 5-HIAA (by 47% at 1 mumol/l). Scopolamine (0.1 mumol/l) did not affect the release of 5-HT and 5-HIAA, but antagonized the effect of oxotremorine. In the presence of TTX (1 mumol/l), oxotremorine (1 mumol/l) increased the release of 5-HT by 150% and that of 5-HIAA by 220%. This increase was completely blocked by scopolamine. Hexamethonium (100 mumol/l) and TTX…
The effects of racemic bethanechol and its (R)- and (S)-enantiomers on pre- and postjunctional muscarine receptors in the guinea-pig ileum
1985
The effect of racemic bethanechol and its (R)- and (S)-enantiomers on smooth muscle contraction and outflow of [3H]-acetylcholine were studied in the guinea-pig myenteric plexus-longitudinal muscle preparation that had been preincubated with [3H]-choline. (S)-, racemic, and (R)-bethanechol caused concentration-dependent contractions of the longitudinal muscle. The potency ratio of the strong isomer (S) to the weak one (R) was 915. Racemic and (S)-bethanechol concentration-dependently inhibited the evoked outflow of [3H]-acetylcholine. Racemic bethanechol was more potent than (S)-bethanechol. (R)-bethanechol up to a concentration of 1 mM did no affect the evoked outflow of [3H]-acetylcholine…
Modulation by 5-HT3 and 5-HT4 receptors of the release of 5-hydroxytryptamine from the guinea-pig small intestine.
1993
The effects of agonists and antagonists of 5-hydroxytryptamine (5-HT) receptors on the release of endogenous 5-HT from enterochromaffin cells were studied in the vascularly perfused isolated guinea-pig small intestine. The experiments were done in the presence of tetrodotoxin in order to exclude a neuronally mediated influence on 5-HT release. The 5-HT3 receptor agonist 2-methyl-5-HT increased 5-HT release, and this effect was antagonized by 1 nmol/l tropisetron. Nanomolar concentrations of tropisetron, MDL 72,222 and granisetron decreased 5-HT release. Ondansetron (0.1 and 1 mumol/l) did not modify 5-HT release. 5-Methoxytryptamine, BIMU8 and cisapride concentration-dependently inhibited 5…
Effects of 5-HT4 receptor stimulation on basal and electrically evoked release of acetylcholine from guinea-pig myenteric plexus
1992
The effects of 5-methoxytryptamine and 5-hydroxytryptamine (5-HT) on both basal and electrically evoked outflow of tritium were studied in guinea-pig myenteric plexus preparations preincubated with [3H]-choline. Basal outflow. 5-Methoxytryptamine caused a transient and calcium-dependent increase in basal outflow of [3H]acetylcholine that was abolished by tetrodotoxin. Ondansetron (1 μmol/1) did not affect the stimulatory response of 5-methoxytryptamine but ICS 205-930 (1 and 3 μmol/1) produced parallel rightward displacements of the concentration-response curve to 5-methoxytryptamine. The PKB value for ICS 205-930 was 6.6 suggesting an involvement of 5-HT4 receptors. 5-HT caused an increase…
PACAP induces bradycardia in guinea-pig heart by stimulation of atrial cholinergic neurones
1996
Based on previous studies which indicated that pituitary adenylate cyclase activating peptide (PACAP) acts as a positive inotropic and chronotropic substance in different species via the cAMP signal transduction pathway, the objective of the present work was to investigate cAMP-regulated myocardial key proteins in response to PACAP in isolated ventricular cells of the guinea pig. Surprisingly, the two molecular forms of PACAP, PACAP(1-27) and PACAP(1-38), showed no effect on intracellular cAMP-levels, L-type Ca2+ channel current or phosphorylation of troponin inhibitor (TnI) and phospholamban (PLB). Additionally, inotropy of isolated guinea-pig ventricular strips was not affected by the neu…
Characterization of the muscarinic receptor subtype(s) mediating contraction of the guinea-pig lung strip and inhibition of acetylcholine release in …
1997
1 The muscarinic receptor subtypes mediating contraction of the guinea-pig lung strip and inhibition of the release of acetylcholine from cholinergic vagus nerve endings in the guinea-pig trachea in vitro have previously been characterized as M-2-like, i.e. having antagonist affinity profiles that are qualitatively similar but quantitatively dissimilar compared to cardiac M-2 receptors. The present study sought to establish definitely the identity of these receptor subtypes by using the selective muscarinic receptor antagonist, tripitramine. Guinea-pig atria and guinea-pig trachea (postjunctional contractile response) were included for reference.2 It was found that tripitramine antagonized …
Evidence that neuronally released vasoactive intestinal polypeptide inhibits the release of serotonin from enterochromaffin cells of the guinea pig s…
1991
Abstract. Isolated small intestinal segments of the guinea pig were arterially perfused and the release of serotonin (5-hydroxytryptamine) and 5-hydroxyindoleacetic acid into the portal venous effluent was determined by HPLC with electrochemical detection. Test substances were intra-arterially applied. The muscarine receptor agonist oxotremorine (1 μmol/l inhibited the release of 5-hydroxytryptamine by about 50%. In the presence of the neurotoxin tetrodotoxin, oxotremorine enhanced the release of 5-hydroxytryptamine by 145%, indicating that the inhibitory effect of oxotremorine was mediated by the release of a neurotransmitter. Exogenous vasoactive intestinal polypeptide ( 1-100 pmol/l inhi…
The inhibition by dopamine of cholinergic transmission in the isolated guinea-pig ileum. Mediation through alpha-adrenoceptors.
1982
1. Segments of the guinea-pig ileum were incubated in Tyrode's solution containing 3 μM propranolol. Dopamine, like noradrenaline and clonidine, inhibited the twitch response to field stimulation. The inhibitory action of dopamine remained unchanged in the presence of the dopamine uptake inhibitor nomifensine (1 μM). Tissue from reserpine-pretreated amimals was insensitive to tyramine but the response to dopamine was not affected. It is, therefore, assumed that the effect of dopamine is due to a direct receptor stimulation and not to the release of noradrenaline. 2. The inhibitory action of dopamine was not antagonized by the dopamine receptor antagonists cis-flupenthixol, pimozide or dompe…