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Biomedical subjects

E Muscholl

Publications and source records attributed to E Muscholl.

At least 55 records · Page 3Linked to original sources
PubMed1976

The effects of methacholine and calcium deprivation on the release of the false transmitter, alpha-methyladrenaline, from the isolated rabbit heart.

1. Anaesthetized rabbits were infused for 20 min with 85 mug-kg-1-min-1(+/-)-alpha-methyladrenaline. The hearts dissected 15 min after the infusion contained 1.49 mug/g alpha-methyladrenaline; the endogenous noradrenaline content was correspondingly decreased. 2. Hearts from alpha-methyladrenaline-infused animals were isolated with the right sympathetic nerves intact and perfused. Ventricular rate, right atrial and right ventricular tensions were recorded using the transverse method. 3. Electrical stimulation (10 Hz, 1 ms, 1 min) of sympathetic nerves, perfusion with the nicotinic drug, p-aminophenethyltrimethylammonium (PAPETA) or perfusion with 54 mM KCl (high K+) solution evoked an output of both alpha-methyladrenaline and noradrenaline. The ratio of the amines in the perfusates was similar to that found in the hearts after termination of the experiments or in non-perfused hearts. 4. Methacholine perfused before and during sympathetic nerve stimulation, PAPETA or high K+ inhibited the release of both false transmitter and noradrenaline. These effects were reversed by atropine. Similarly, lowering the calcium chloride concentration of the medium from 1.8 to 0.1 mM decreased amine outputs. This was reversed by washing. 5. Tyramine evoked a preferential release of the false transmitter that was not altered by methacholine or calcium deprivation. 6. These experiments whow that the muscarinic inhibition of neuronal noradrenaline release and the requirement of calcium ions for its liberation by depolarizing stimuli can be extended to a false transmitter amine. It is suggested that the proportion of alpha-methyladrenaline to noradrenaline occurring in the perfusate during administration of tyramine reflects the relative concentrations of the amines in the axoplasm.

Aniline Compounds↗
PubMed1975

Absence of muscarinic modulation of vasopressin release from the isolated rat neurophypophysis.

1. Isolated rat neurohypophyses were incubated in Locke solution at 37 degress 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 5.5x10-4M neither alone nor in the presence of atropine 2.9x10-6M changed the "resting" release of vasopressin. 4. Neither acetylcholine 5.5x10-4M oxotremorine 10-4 and k3x10-4M 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 appear to contain muscarinic inhibitory or nicotinic excitatory receptors.

Acetylcholine↗
PubMed1975

Arrhythmias and inhibition of noradrenaline uptake caused by tricyclic antidepressants and chlorpromazine on the isolated perfused rabbit heart.

1. Isolated rabbit hearts were perfused with a modified Tyrode solution containing noradrenaline in concentrations increasing stepwise from 5.9 nM to 5.9 muM at 5 min intervals. This dose regime was applied twice before and once 20 min after starting perfusion with one of 9 tricyclic drugs. Ventricular rate and right atrial and ventricular tensions were recorded using the transverse method. 2. Infusions of noradrenaline evoked ventricular arrhythmias in hearts perfused with amitriptyline 4.8 muM, chlorpromazine 5.0 muM, desipramine 5.0 muM, dibenzepine 34.7 muM, doxepin 4.7 muM, imipramine 4.7 muM, noxiptiline 9.1 muM and opipramole 9.2 muM. The incidence of arrhythmias increased with the concentration of noradrenaline applied and the dose of tricyclic drug administered. Whenever arrhythmias had started they continued as long as noradrenaline was infused. Noradrenaline failed to produce arrhythmias in hearts not exposed to drugs and after iprindole 4.7 muM or cocaine 2.9-18 muM. 3. Propranolol 0.1 muM inhibited the incidence of arrhythmias after doxepin 4.7 muM plus noradrenaline 5.9-190 nM. 4. Neuronal uptake of exogenous noradrenaline in the rabbit heart was inhibited by the tricyclic drugs in the following order of declining p potency: doxepin, noxiptiline, amitriptyline, desipramine, chlorpromazine, imipramine, dibenzepine, opipramole and iprindole. 5. Among tricyclic drugs the potency to inhibit amine uptake is related to the incidence of arrhythmias evoked by a submaximal concentration of noradrenaline. It appears, however, that these two parameters are not causally linked. 6. The isolated rabbit heart perfused with noradrenaline might be used as a model for testing the arrhythmogenic actions of tricyclic drugs and the treatment of such arrhythmias.

Animals↗
PubMed1975

Muscarinic inhibition of potassium-induced noradrenaline release and its dependence on the calcium concentration.

1. Noradrenaline release from the isolated rabbit heart was evoked by perfusion with a medium containing 135 mM potassium and 17 mM sodium ions (high K+-low Na+). 2. The noradrenaline output in response to high K+-low Na+ was dose-dependently decreased by methacholine (0.625-320 muM) and this effect was reserved by atropine 1.44 mM. 3. Lowering the calcium concentration of high K+-low Na+ from 1.8-0.1125 mM decreased the noradrenaline output by 85%. The effect of methacholine, expressed as % inhibition of noradrenaline release, was potentiated by lowering of the calcium concentration. 4. Both at normal and lowered calcium concentrations the inhibitory action of methacholine was larger from 0-5 than from 5-10 min after perfusion with high K+-low Na+. 5. Perfusion of hearts with media containing high K+-low Na+ or normal K+-low Na+ caused noradrenaline outputs somewhat smaller than those after high K+-low Na+. The release from 0-5 min was both calcium-dependent and inhibited by methacholine. 6. High K+ and/or low Na+ solutions caused an increase in coronary perfusion pressure which was little affected by the noradrenaline released simultaneously. 7. It is concluded that activation of muscarine receptors at the terminal adrenergic fibre decreases the availability of calcium for transmitter release.

Animals↗
PubMed1974

Atropine-resistant effects of the muscarinic agonists McN-A-343 and AHR 602 on cardiac performance and the release of noradrenaline from sympathetic nerves of the perfused rabbit heart.

1 The effects of 4-(m-chlorophenylcarbamoyloxy)-2-butynyltrimethylammonium chloride (McN-A-343) and N-benzyl-3-pyrrolidyl acetate methobromide (AHR 602) on cardiac performance and noradrenaline release from terminal sympathetic fibres were measured in isolated perfused hearts of rabbits.2 In the presence of sufficient atropine to block muscarinic receptors, high concentrations of McN-A-343 and AHR 602 caused no cardiac stimulation and there was no increase in the resting output of noradrenaline into the perfusates.3 McN-A-343 and AHR 602 increased both the mechanical responses and the transmitter overflow evoked by electrical stimulation of the sympathetic nerves (SNS) but inhibited both parameters during perfusion with 1,1-dimethyl-4-phenylpiperazinium (DMPP). The effects were atropine-resistant and qualitatively similar to those seen with cocaine. Hexamethonium inhibited DMPP, but affected neither SNS per se nor the facilitatory effects of McN-A-343 and AHR 602 on SNS.4 McN-A-343, cocaine and desipramine (but not AHR 602 or hexamethonium) blocked the net cardiac noradrenaline uptake and increased the positive chronotropic effect of noradrenaline.5 Prior perfusion with concentrations of cocaine and desipramine sufficient to block uptake reduced or abolished the facilitatory effects of both McN-A-343 and AHR 602 on SNS.6 Cocaine, McN-A-343 and AHR 602 displayed local anaesthetic properties on the guinea-pig wheal and frog nerve plexus tests, and their relative potencies in this respect were similar to those for inhibition of DMPP-evoked transmitter overflow. Hexamethonium did not produce local anaesthesia.7 The results indicate that the facilitated release of noradrenaline after SNS and the inhibition of release after DMPP produced by McN-A-343 and AHR 602 are the result of their combined local anaesthetic action and inhibition of amine uptake.

Acetylcholine↗
PubMed1972

Effects of several muscarinic agonists on cardiac performance and the release of noradrenaline from sympathetic nerves of the perfused rabbit heart.

1. The effects of several muscarinic agonists on atrial tension development, ventricular rate and noradrenaline release from terminal sympathetic fibres evoked by electrical nerve stimulation (SNS) and 1,1-dimethyl-4-phenylpiperazinium (DMPP) were measured in isolated perfused rabbit hearts.2. Hexamethonium, in a concentration which almost abolished the release of noradrenaline by DMPP, had no effect on the release produced by SNS, confirming that the stimulation was postganglionic.3. The order of potency for inhibition of atrial tension development was N-methyl-1,2,5,6, tetrahydro-nicotinic acid prop-2-yne ester (MH-1)>oxotremorine > acetylcholine > methacholine > carbachol > furtrethonium > pilocarpine>4-(m-chlorophenylcarbamoyloxy)-2-butynyltrimethylammonium chloride (McN-A-343)>N-benzyl-3-pyrrolidyl acetate methobromide (AHR 602). All effects were abolished by atropine (1.4 x 10(-6)M).4. Each compound was more potent relative to acetylcholine in inhibiting ventricular rate than atrial tension. With the exception of carbachol, the order of potency was the same.5. Both AHR 602 and McN-A-343 facilitated the release of noradrenaline by SNS and inhibited that by DMPP. The effects were atropine-resistant and hence non-muscarinic.6. The muscarinic compounds (except AHR 602 and McN-A-343) each produce atropine-sensitive inhibition of noradrenaline release evoked both by SNS and DMPP although it is likely that furtrethonium and pilocarpine have additional non-muscarinic inhibitory activity against DMPP. The order of potency on both parameters and the potencies relative to acetylcholine were in good agreement with those for inhibition of atrial tension.7. The results suggest that similar muscarinic receptors mediate inhibition of atrial tension development, ventricular rate and neuronal noradrenaline release caused by SNS and DMPP.8. In terms of the two muscarinic sites known to be present in the superior cervical ganglion, the receptors of the terminal fibres mediating inhibition of noradrenaline release are more likely to correspond to those mediating hyperpolarization than to those mediating depolarization, for which AHR 602 and McN-A-343 show specificity.

Acetylcholine↗