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

Abstract

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.