Inhibitory and excitatory muscarinic receptors modulating the release of acetylcholine from the postganglionic parasympathetic neuron of the chicken …

1992

The effects of muscarinic receptor antagonists on ACh release were studied in the absence or presence of cholinesterase (ChE) inhibition using the isolated perfused chicken heart. Presynaptic inhibitory muscarinic autoreceptor were characterized by determining the potency of various antagonists to enhance [3H]-ACh release evoked by field stimulation (3 Hz, 1 min). The order of potencies was: (±)-telenzepine > atropine > 4-DAMP > silahexocyclium > pirenzepine > hexahydro-siladifenidol > AF-DX 116. The comparison with known pA2 values for M1-, M2- and M3-receptors revealed that the presynaptic autoreceptor meets the criteria of an M1-receptor. Basal, not electrically evoked overflow of unlabe…

The neuronal efflux of noradrenaline: Dependency on sodium and facilitation by ouabain

1974

Rabbit hearts were isolated after pretreatment with the MAO inhibitor pargyline and with reserpine and were perfused with 200 ng/ml noradrenaline for 1 h. During the subsequent wash-out with an amine-free solution for 2 h, the neuronal efflux of noradrenaline declined mono-exponentially with a mean halftime of 42 min. Both Na+-free solution and ouabain caused facilitation of the efflux which thereafter declined in a multi-exponential fashion. The maximum facilitation was reached after 3 min of Na+-free perfusion and 25 min after introduction of ouabain. The amount of exogenous noradrenaline accumulated in the heart was only partially released when the extracellular Na+-concentration was nor…

Die Wirkung von 1,1-Dimethyl-4-Phenyl-Piperazinium-Jodid am isolierten Vorhof im Vergleich zur Tyramin- und Nicotinwirkung

1962

Evidence for noradrenaline and adrenaline as sympathetic transmitters in the chicken.

1975

1 The concentrations of noradrenaline and adrenaline in various organs, arterial plasma and venous outflow from isolated hearts of adult chickens have been determined. 2 The relative adrenaline concentrations (percentage of the sum of noradrenaline and adrenaline) in the heart (33%), spleen (16%) and brain (26%) were higher than those found in mammalian organs. Chemical sympathectomy by pretreatment with 6-hydroxydopamine caused a decrease of the noradrenaline and adrenaline concentrations in the heart to 20 and 23% and in the spleen to 16 and 29%, respectively. 3 Stimulation of the right sympathetic nerves, infusion of tyramine or infusion of a modified Tyrode solution containing 108mM K+ …

Muscarinic Receptor Activation Increases Efflux of Choline from Isolated Heart and Rat Cortex in Vivo. Interactions with Forskolin and IBMX

1986

Muscarinic receptor activation modulates functions of the heart and neurotransmission in the peripheral and central nervous system. Moreover, muscarinic agonists produce changes in the metabolism of, for example, heart tissue, such as inhibition of beta-adrenoceptor-mediated cAMP accumulation, glycogenolysis and lipase activation.

Die Wirkung von Cocain, Guanethidin, Reserpin, Hexamethonium, Tetracain und Psicain auf die Noradrenalin-Freisetzung aus dem Herzen

1961

Short- and long-term effects of vinblastine on the rat adrenal medulla

1979

The effects of a single high dose (10mg/kg) of vinblastine (vb) sulfate (“Velbe”, Lilly) on the ultrastructure, catecholamine (CA) content and activity of CA-synthesizing enzymes of the rat adrenal medulla were studied for up to 120h after intravenous injection of the drug.

Unterschiede zwischen Tyramin und Dimethylphenylpiperazin in der Ca++-Abhängigkeit und im zeitlichen Verlauf der Noradrenalin-Freisetzung am isoliert…

1967

On the perfused rabbit heart a constant infusion of tyramine released noradrenaline continuously and independently of the external Ca++ concentration. In contrast, noradrenaline release by DMPP was only transient and required the presence of Ca++.

Interstitial washout and hydrolysis of acetylcholine in the perfused heart

1982

The efflux of acetylcholine, of radioactively labelled acetylcholine and choline, into the venous effluent of the perfused chicken heart was studied to determine the kinetics of both interstitial washout and hydrolysis of acetylcholine. Stimulation of both cervical vagus nerves (e.g., for 5 s at 40 Hz) caused a release of acetylcholine, which appeared partially unhydrolyzed in the venous effluent, and reduced force of contraction and heart rate. For comparison, labelled acetylcholine or choline was infused for 5 s into the heart and again the venous efflux of either substance was determined. It was found that the kinetics of efflux of acetylcholine or choline from the interstitial space wer…

Die Ausscheidung von Katecholaminen und Aminmetaboliten von α-Methyldopa in den Harn zu verschiedenen Zeitpunkten nach der letzten verabreichten Dosis

1969

Die Wirkung von Pharmaka auf die Elimination von Noradrenalin aus der Perfusionsfl�ssigkeit und die Noradrenalinaufnahme in das isolierte Herz

1964

The release of choline from phospholipids mediated by beta-adrenoceptor activation in isolated hearts.

1986

The resting efflux of choline into the perfusate (Tyrode's solution) of isolated hearts was equal to the rate, at which choline was liberated from phospholipid degradation (Lindmar et al. 1986). Infusion of isoprenaline (2 X 10(-7) mol/l), forskolin (1-3 X 10(-6) mol/l) or 3-isobutyl-1-methylxanthine (IBMX; 3 X 10(-4) mol/l) for 40 min markedly enhanced the efflux of choline. The increase was linear during the experimental period and, in the case of isoprenaline, was blocked by 3 X 10(-7) mol/l atenolol. In the guinea-pig heart, IBMX at a threshold concentration of 10(-4) mol/l shifted the concentration-response curve for the effect of forskolin on the efflux of choline to the left by one l…

Characterization of choline efflux from the perfused heart at rest and after muscarine receptor activation.

1986

The resting efflux of choline from perfused chicken hearts varied from 0.4 to 2.6 nmol/g min, but was constant for at least 80 min in the individual experiments. The rate of choline efflux was found to be equal to the rate of choline formation in the heart, which, from the following reasons, was essentially due to hydrolysis of choline phospholipids. Cardiac content of choline phospholipids (7,200 nmol/g) was much higher than that of acetylcholine (5.5 nmol/g). Resting release of acetylcholine was 0.016 nmol/g min and, after inhibition of cholinesterase, only about 0.1 nmol/g min. Resting efflux of choline was reduced by mepacrine, a phospholipase A2 inhibitor, by perfusion with a Ca2+-free…

Der Einflu� von Reserpin auf die Wirkung der ?Neuro-Sympathomimetica?

1960

Die Aufnahme von ?-Methylnoradrenalin in das isolierte Kaninchenherz und seine Freisetzung durch Reserpin und Guanethidin in vivo

1965

Aufnahme von Guanethidin in Gewebe nach sympathischer Denervierung und Vorbehandlung mit Reserpin

1964

Aufnahme von threo-Corbadrin und seine Freisetzung als falsche sympathische �bertr�gersubstanz

1968

The effect of tacrine on acetylcholine overflow in the heart

1990

Tacrine, 10(-6) M, enhanced the acetylcholine (ACh) overflow evoked in perfused chicken hearts by field stimulation (5 Hz, 1 min) from 183 to 346 pmol g-1 min-1. Increase to the same level were observed after pretreatment with diisopropylfluorophosphate (DFP) as well as after DFP plus 10(-6) M tacrine. Tacrine, 10(-5) M, caused further enhancement with or without DFP up to 851 pmol g-1 min-1. It was concluded that 10(-6) M tacrine enhanced the ACh overflow by choline esterase inhibition, whereas 10(-5) M tacrine caused, in addition, an increase of neuronal ACh release.

Acetylcholine overflow during infusion of a high potassium-low sodium solution into the perfused chicken heart in the absence and presence of physost…

1977

1. The effect of infusion of a modified Tyrode's solution (“high K+-low Na+ solution”) into the isolated chicken heart on the content of acetylcholine in the tissue and the overflow of acetylcholine were compared to those evoked by vagal stimulation. 2. The release of acetylcholine was measured over 15-min periods of either stimulation of the vagus nerves (40 V, 1 ms) at 20 Hz or of infusion of the high K+-low Na+ solution (108 mM K+, 44 mM Na+). 3. Both stimuli caused a maximum overflow of acetylcholine in the first few minutes whether or not 10−6 M physostigmine was present. The overflow was maintained during the vagal stimulation at a constant rate of at least 35% the initial rate, where…

Ouabain enhances release of acetylcholine in the heart evoked by unilateral vagal stimulation.

1986

The aim of the study was to elucidate peripheral effects of ouabain on the parasympathetic innervation of the heart, effects that could contribute to the experimentally and clinically well established “vagal effect of cardiac glycosides”. The experiments were carried out with ouabain concentrations of 3×10−7 and 10−6 mol/l, which were considered “therapeutic”, as they increased force of contraction and did not elicit arrhythmias in incubated chicken atria. In atrial preparations of chickens and guinea-pigs the negative chronotropic and inotropic effects of acetylcholine (ACh) were not altered by 3×10−7 mol/l ouabain. Resting efflux of ACh from perfused chicken hearts was increased by ouabai…

Evidence for bilateral vagal innervation of postganglionic parasympathetic neurons in chicken heart

1983

Stimulation of the cervical vagus nerves caused an output of acetylcholine (ACh) from the isolated chicken heart, which almost exclusively was released from the postganglionic neurons: (+)-tubocurarine (3 X 10(-14) M) reduced the output to 12 +/- 6% (n = 7) of the control. Stimulation of the two nerve trunks ws equally effective in releasing ACh.--Evidence that a large number of postganglionic neurons receives bilateral innervation was based on two experimental series. (1). The sum of the ACh outputs evoked by unilateral (separate) nerve stimulation of the right and the left vagus was higher than the bilaterally evoked output (100%) and increased with increasing frequencies (10, 20 and 40 H…

The interferance of muscarinic receptors with the noradrenaline release from sympathetic nerve endings caused by nicotinic agents.

1968

Funktionelle Bedeutung der Freisetzung von Dihydroxyephedrin und Dihydroxypseudoephedrin als ?falschen? sympathischen �bertr�gerstoffen am Herzen

1967

The experiments were carried out in order to investigate the functional significance of substitution of noradrenaline by amines known to exert actions weaker than those of the natural transmitter. On the isolated rabbit heart the potency relative to noradrenaline of (±)-dihydroxyephedrine to increase the rate was 1/4 and the potency to augment the contractile amplitude was 1/6. The corresponding values for (±)-dihydroxypseudoephedrine were 1/67 and 1/140, respectively.

Freisetzung von Alpha-Methylnoradrenalin durch sympathische Aktivität beim Menschen nach Verabreichung von Alpha-Methyldopa

1968

Nach dem Ergebnis von Tierversuchen wird Alpha-Methyldopa im Organismus zu Alpha-Methyldopamin dekarboxyliert. Dieses Amin wird dann zu Alpha-Methylnoradrenalin hydroxyliert und in sympathischen Nerven zusammen mit dem naturlichen Ubertragerstoff Noradrenalin gespeichert (Carlsson u. Lindqvist, 1962). Da Alpha-Methylnoradrenalin bei elektrischer oder pharmakologischer Reizung sympathischer Nerven zusammen mit Noradrenalin freigesetzt wird (Musduoll u. Maitre, 1963), bezeichnet man es auch als „falschen“ sympathischen Ubertragerstoff. Einer Hypothese von Day U. Rand (1964) zufolge wird auch am Menschen bei antihypertensiver Therapie mit Alpha-Methyldopa das Alpha-Methylnoradrenalin gebildet …

A muscarinic mechanism inhibiting the release of noradrenaline from peripheral adrenergic nerve fibres by nicotinic agents.

1968

Wirkungen von threo-1-(3,4-Dihydroxyphenyl)-1-hydroxy-2-aminopropan, dem Diastereomeren von Corbadrin

1967

Phorbol Esters and Muscarinic Receptor Agonists Activate Phospholipase D in Heart and Brain

1991

Phospholipase D (PLD) hydrolyzes phosphatidylcholine and thereby seems to play a key role in a novel pathway of signal transduction. PLD activity in rat hippocampal slices and atria of rat, guinea pig and chicken hearts was determined by measuring the catalytic products choline (Ch), phosphatidic acid (PA) and, in the presence of a primary alcohol, phosphatidylpropanol or phosphatidylethanol. It was found that the PLD activity was high, even under resting conditions, in both tissues, especially in the hippocampus, and that the enzyme activity could be enhanced by activation of protein kinase C and by muscarinic receptor stimulation.

Subtypes of muscarinic receptor on cholinergic nerves and atrial cells of chicken and guinea-pig hearts

1988

1. Electrically driven chicken and guinea-pig atria were used to investigate the negative inotropic effects of the muscarinic agonists methacholine and acetylcholine (ACh). The release of ACh from isolated hearts into the perfusate in response to (preganglionic) vagal or (pre- and postganglionic) field stimulation was bioassayed on the guinea-pig ileum or determined by labelling with [3H]-choline. 2. Concentration-response curves for the negative inotropic effect of methacholine were shifted to the right by pirenzepine in various concentrations (0.03 to 10 mumol l-1). The pA2 values were 7.76 in chicken atria and 6.53 in guinea-pig atria. Pirenzepine and atropine antagonized the negative in…

Regulation of Acetylcholine Synthesis and Release in the Isolated Heart

1981

In the two decades following Loewi’s work (8,9) on the frog heart several research groups tried to use the isolated heart preparation from higher vertebrates for further investigations on synthesis, release and inactivation of acetylcholine (ACh). However the results were discouraging because the overflow of ACh during vagal stimulation was near, or below, the limit of the assay.

Wirkung von Reserpin auf im Herzen gespeichertes α-Methylnoradrenalin

1964

Muscarinic mobilization of choline in rat brain in vivo as shown by the cerebral arterio-venous difference of choline.

1987

In anesthetized rats, the choline levels of cerebrospinal fluid and plasma obtained from blood collected from peripheral vessels (carotid artery, cardiac vessels) and from the transverse sinus were determined with a radioenzymatic assay. Cortical release of choline was studied using the "cup technique." The plasma choline level of the peripheral blood (11.5 mumol/L) was lower than that of the sinus blood. The resulting cerebral arterio-venous difference of choline was negative (3.2 mumol/L) and reflected the net release of choline from the whole brain. The plasma choline levels were not different irrespective of whether the rats were anesthetized with ether, urethane, or pentobarbital. Howe…

Die Freisetzung von Noradrenalin aus dem perfundierten Kaninchenherzen

1961

Differential effects of hypothermia on neuronal efflux, release and uptake of noradrenaline

1972

Isolated rabbit hearts were perfused at 34° (control), 24° or 12°C. The neuronal efflux of noradrenaline after perfusion with the amine for 1 h was depressed at 24° C (Q 10 about 5) in the presence or absence of desipramine; at 12°C the efflux was below the limit of estimation. Moderate reduction of the temperature (24° C) decreased the removal of perfused noradrenaline to about 60% of the control value and caused a 1.7-fold increase of the output of noradrenaline evoked by sympathetic nerve stimulation. It is concluded that the extremely temperature-dependent efflux of noradrenaline across the axonal membrane is not part of the release of noradrenaline evoked by nerve stimulation.

The effects of phorbol esters on choline phospholipid hydrolysis in heart and brain

1990

The efflux of choline was determined in rat striatal slices, incubated chicken atria and perfused chicken hearts. 4 beta-Phorbol-12 beta,13 alpha-dibutyrate (PDB) and 4 beta-phorbol-12 beta-myristate, 13 alpha-acetate (PMA) were used to stimulate protein kinase C. The other phorbol esters, 4 beta-phorbol-13 alpha-acetate (PAc) and 4 alpha-phorbol-12 beta,13 alpha-didecanoate (4 alpha PDD), known to be inactive, were tested to evaluate the specificity of the responses. PDB markedly enhanced the efflux of choline in all of the three preparations. The PDB-evoked efflux of choline in incubated chicken atria was equal to the net production of choline and, therefore, was not caused by translocati…

Neuronal and extraneuronal uptake and efflux of catecholamines in the isolated rabbit heart

1974

1. Isolated rabbit hearts were perfused with (−)-noradrenaline, (−)-adrenaline and (±)-isoprenaline for various time periods (1–180 min) and then washed with an amine-free medium. The venous concentration of the amine was estimated fluorimetrically during the infusion and after its end, to study removal and efflux, respectively. 2. In untreated hearts and after pretreatment with reserpine the removal had a constant rate over 20–60 min. After pretreatment with pargyline to block monoamine oxidase (MAO), however, the removal of noradrenaline declined exponentially to zero. Inhibition of the neuronal uptake (desipramine) and chemical sympathectomy (6-hydroxydopamine) abolished the removal of n…

DMPP and the adrenergic nerve terminal: mechanisms of noradrenaline release from vesicular and extravesicular compartments.

1977

DMPP (1,1-dimethyl-4-phenylpiperazine) in various concentrations between 1.6×10−6 M and 6.2×10−5 M was infused into isolated rabbit hearts to study the neuronal release and uptake of noradrenaline.

Phospholipase D in heart: basal activity and stimulation by phorbol esters and aluminum fluoride

1992

Evidence for a general role of phospholipase D in signal transduction is accumulating. In the present study, the activity of the enzyme was investigated in heart tissue under basal conditions and after addition of phorbol esters or aluminum fluoride (AlF inf4 sup− ; 10 mM NaF plus 10 μM AlCl3). Atria of rats and chickens were incubated with [3H]-myristic acid in order to label preferentially phosphatidylcholine. Under basal conditions, the tissues generated choline and phosphatidic acid (PtdOH), the primary catalytic products of phospholipase D. When 0.5 or 2.0% ethanol was present, [3H]-phosphatidyl-ethanol (PETH) was rapidly formed at the expense of [3H]-PtdOH. This transphosphatidylation…

Noradrenaline depleting and blood pressure lowering activity of threo-corbadrine

1968

Abstract Threo-corbadrine caused a long-lasting depletion of noradrenaline in the heart and in mesenteric vessels and lowered the blood pressure of normal and renal hypertensive rats. It is suggested that threo-cobadrine decreases vascular tone by acting peripherally as a substitute adrenergic transmitter.

Wirkungen von threo-Corbadrin auf die Aminspeicher und den Blutdruck der Ratte

1968

Storage and release of false transmitters after infusion of (+)- and (?)-?-methyldopamine

1971

Rabbits were given an infusion of 10 mg/kg (−)- or 30 mg/kg (+)-α-methyldopamine and killed after 135 min. The noradrenaline content of the heart was decreased to 26±5 and 34±2%, respectively, of the control value. After infusion of the (+)-isomer the missing noradrenaline was replaced by (−)-α-methylnoradrenaline. Electrical stimulation of the sympathetic nerves or infusion of acetylcholine plus atropine caused an output of noradrenaline and (−)-α-methylnoradrenaline from the isolated heart. The two amines were released in the same proportion as they were stored in the heart and the total output of both amines equalled the output of noradrenaline from control hearts. Nerve stimulation caus…

Phospholipase D in rat myocardium: formation of lipid messengers and synergistic activation by G-protein and protein kinase C.

1998

Activation of phospholipase D (PLD) and phosphoinositide-specific phospholipase C (PI-PLC) by fluoride, to stimulate heterotrimeric G-proteins, and by phorbol esters, to stimulate protein kinase C (PKC), was studied in rat atria. Fluoride and 4beta-phorbol-12beta,13alpha-dibutyrate (PDB), in contrast to 4beta-phorbol-13alpha-acetate (PAc), activated PLD, catalyzing the formation of [3H]-phosphatidylethanol ([3H]-PETH), [3H]-phosphatidic acid ([3H]-PA), choline and sn-1,2-diacylglycerol (DAG). Basal PLD activity was resistant to drastic changes in Ca2+ and to Ro 31-8220, a PKC inhibitor, but was decreased by genistein, an inhibitor of tyrosine kinase, and increased by vanadate, a tyrosine ph…

PRECURSOR CONTROL OF ACETYLCHOLINE SYNTHESIS AND RELEASE IN ISOLATED HEARTS ?

1980

The role of choline in the release of acetylcholine in isolated hearts.

1978

1. The concentrations of acetylcholine, choline and noradrenaline were estimated in the perfusate (overflow) of isolated hearts of chickens, cats, rabbits and guinea pigs. Neurotransmitter release was evoked by stimulation of both vagus nerves and by direct stimulation of the heart (field stimulation). 2. In the absence of exogenous choline and physostigmine, field stimulation at 20 Hz for 20 min caused an overflow of acetylcholine from the hearts of the 4 species investigated. During vagal stimulation, however, acetylcholine was detected only in the perfusate of the chicken heart. 3. Field stimulation for 2 min caused an overflow of 193 pmol g−1 min−1 acetylcholine and of 666 pmol g−1 min−…