0000000000124450
AUTHOR
H. Schwörer
Effects of dopamine infusion on plasma catecholamines in preterm and term newborn infants.
Newborn infants (21 preterm and 13 term) received dopamine infusions at a low (2.5-3.4 micrograms/kg per min) and/or high (5-10 micrograms/kg per min) infusion rate and changes in plasma catecholamines were monitored. The mean baseline values for dopamine, noradrenaline and adrenaline were between 240 and 560, 125 and 144 and 62 and 82 pg/ml, respectively. During low-rate infusion of dopamine, there was a significant increase in plasma dopamine (20-100 fold), noradrenaline (three- to five-fold) and adrenaline (threefold). Administration of dopamine at the high rate resulted in an even larger increase in the plasma catecholamines (dopamine, 100-300 fold; noradrenaline, seven- to eightfold; a…
Muscarinic modulation of acetylcholine release: Receptor subtypes and possible mechanisms
The release of acetylcholine from central and peripheral neurones can be inhibited and facilitated by muscarine autoreceptors, i.e. receptors located on the cholinergic neurone. In the last few years evidence has accumulated that muscarine receptors are heterogeneous. This chapter describes attempts that have been made to classify the muscarine autoreceptors. In addition, some possible mechanisms behind the neuronal muscarine receptors are examined.
Enhancement of guinea-pig intestinal peristalsis by blockade of muscarinic M1-receptors
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
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…
Characterization of the muscarine receptors involved in the modulation of serotonin release from the vascularly perfused small intestine of guinea pig.
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…
Cisplatin increases the release of 5-hydroxytryptamine (5-HT) from the isolated vascularly perfused small intestine of the guinea-pig: Involvement of 5-HT3 receptors
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-…
Effect of vasoactive intestinal polypeptide on the release of serotonin from the in vitro vascularly perfused small intestine of guinea pig.
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…
Effects of cromakalim on acetylcholine release and smooth muscle contraction in guinea-pig small intestine
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…
Effects of cigarette smoking or ingestion of nicotine on platelet 5-hydroxytryptamine (5-HT) levels in smokers and non-smokers.
Platelets of healthy smokers and non-smokers were prepared and their content of 5-hydroxytryptamine was determined by HPLC with electrochemical detection. Platelet 5-HT levels in smokers (728 +/- 156 pmol per 10(8) platelets, mean +/- SEM, n = 9) were significantly higher than those in non-smokers (353 +/- 156 pmol per 10(8) platelets, n = 11). Smoking of a single cigarette caused a transient increase in platelet 5-HT levels by about 350% in non-smokers, but had no additional effect in smokers. Similarly, chewing of nicotine gum (4-8 mg nicotine) resulted in a transient increase in platelet 5-HT by about 100% in non-smokers, but not in smokers. In conclusion, smoking of cigarettes can cause…
Effects of the benzodiazepine receptor agonist midazolam and antagonist flumazenil on 5-hydroxytryptamine release from guinea-pig intestine in vitro
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…
Temperature-dependent effects of increased intraluminal pressure on serotonin release from the vascularly perfused guinea pig ileum
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…
Nicotinic and muscarinic modulation of 5-hydroxytryptamine (5-HT) release from porcine and canine small intestine
Strips of porcine and canine small intestine were incubated in vitro and the release of 5-hydroxytryptamine (5-HT) was determined by HPLC with electrochemical detection. The spontaneous outflow of 5-HT from the porcine and canine small intestine largely reflects calcium-dependent 5-HT secretion from enterochromaffin cells which are under a spontaneous neuronal, excitatory input as indicated by the inhibitory effect (30-40%) of tetrodotoxin. In both species, nicotine enhanced the release of 5-HT in a concentration-dependent manner by a maximum of about 50% at 100 microM. This effect was blocked by the nicotine receptor antagonist hexamethonium, but not by the subtype-selective nicotine recep…
Spontaneous release of endogenous 5-hydroxytryptamine and 5-hydroxyindoleacetic acid from the isolated vascularly perfused ileum of the guinea-pig
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…
Control of Acetylcholine Release and of Intestinal Motility by Subtypes of Muscarine Receptors
Two types of neuronal muscarine receptors have been investigated in the myenteric plexus preparation of the guinea-pig small intestine: 1. Presynaptic receptors activation of which inhibits the depolarization-evoked release of acetylcholine. Pirenzepine and dicyclomine have low affinities to the release-inhibitory receptors (pA2 values 6.9 and 7.6) which suggests that the presynaptic receptors (similar to the smooth muscle receptors) belong to the M2 subtype. The inhibition of the electrically-evoked acetylcholine release by muscarine (0.01 - 1 μmol/1) was not affected by forskolin (1μmol/l). This indicates that cyclic AMP is not crucially involved in the muscarinic inhibition of acetylchol…
Cholinergic modulation of the release of 5-hydroxytryptamine from the guinea pig ileum.
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
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…