Summary
-
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 μM) and this effect was reserved by atropine 1.44 μM.
-
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+-high 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.
Similar content being viewed by others
References
Bogdanski, D. F., Brodie, B. B.: The effects of inorganic ions on the storage and uptake of H3-norepinephrine by rat heart slices. J. Pharmacol. exp. Ther. 165, 181–189 (1969)
Cabrera, R., Torrance, R. W., Viveros, H.: The action of acetylcholine and other drugs upon the terminal parts of the postganglionic sympathetic fibre. Brit. J. Pharmacol. 27, 51–63 (1966)
Carrier, G. O., Matheny, J. L., Ahlquist, R. P.: Autonomic drug-receptor interaction in the presence and absence of extracellular calcium in mammalian myocardium. Arch. int. Pharmacodyn. 212, 185–194 (1974)
Dubey, M. P., Muscholl, E.: Muscarinic inhibition of noradrenaline release evoked by potassium ions. Naunyn-Schmiedeberg's Arch. Pharmacol. 277, Suppl. R 12 (1973)
Fozard, J. R., Muscholl, E.: Effects of several muscarinic agonists on cardiac performance and the release of noradrenaline from sympathetic nerves of the perfused rabbit heart. Brit. J. Pharmacol. 45, 616–629 (1972)
Frankenhaeuser, B., Hodgkin, A. L.: The action of calcium on the electrical properties of squid axons. J. Physiol. (Lond.) 137, 218–244 (1957)
Garcia, A. G., Kirpekar, S. M.: Release of noradrenaline from the cat spleen by sodium deprivation. Brit. J. Pharmacol. 47, 729–747 (1973)
Göthert, M.: Effects of halothane on the sympathetic nerve terminals of the rabbit heart. Differences in membrane actions of halothane and tetracaine. Naunyn-Schmiedeberg's Arch. Pharmacol. 286, 125–143 (1974)
Haeusler, G., Thoenen, H., Haefely, W., Huerlimann, A.: Electrical events in cardiac adrenergic nerves and noradrenaline release from the heart induced by acetylcholine and KCl. Naunyn-Schmiedebergs Arch. Pharmak. exp. Path. 261, 389–411 (1968)
Hedqvist, P.: Interaction between prostaglandins and calcium ions on noradrenaline release from the stimulated guinea pig vas deferens. Acta physiol. scand. 90, 153–157 (1974)
Junstad, M., Stjärne, L., Wennamalm, A.: On the relative importance of extraneuronal uptake of noradrenaline released by nerve stimulation in the rabbit heart. Acta physiol. scand. 88, 67–70 (1973)
Kirpekar, S. M., Wakade, A. R.: Release of noradrenaline from the cat spleen by potassium. J. Physiol. (Lond.) 194, 595–608 (1968)
Lindmar, R., Löffelholz, K., Muscholl, E.: A muscarinic mechanism inhibiting the release of noradrenaline from peripheral adrenergic nerve fibres by nicotinic agents. Brit. J. Pharmacol. 32, 280–294 (1968)
Löffelholz, K., Muscholl, E.: A muscarinic inhibition of the noradrenaline release evoked by postganglionic sympathetic nerve stimulation. Naunyn-Schmiedebergs Arch. Pharmak. 265, 1–15 (1969)
Malik, K. U., Ling, G. M.: Modification by acetylcholine of the response of rat mesenteric arteries to sympathetic stimulation. Circulat. Res. 25, 1–9 (1969)
Muscholl, E.: Muscarinic inhibition of the norepinephrine release from peripheral sympathetic fibres. Proc. 5th Int. Congr. Pharmacology, Vol. 4, pp. 440–457. Basel: Karger 1973a
Muscholl, E.: Regulation of catecholamine release. The muscarinic inhibitory mechanism. Frontiers in Catecholamine Research, pp. 537–542. Oxford: Pergamon Press 1973b
Muscholl, E.: Transmitter release. Introduction. Proc. 2nd Meet. on Adrenergic Mechanisms, Porto, pp. 33–39 (1974)
Scheffé, H.: The analysis of variance. New York-London-Sideny: John Wiley & Sons 1959
Smith, A. D., Winkler, H.: Fundamental mechanisms in the release of catecholamines. Handbook exp. Pharmacol., vol. 33. H. Blaschko and E. Muscholl, eds., pp. 538–617 (1972)
Stjärne, L.: Mechanisms of catecholamine secretion. Dual feedback control of sympathetic neurotransmitter secretion; role of calcium. Frontiers in Catecholamine Research, pp. 491–496. Oxford: Pergamon Press 1973
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Dubey, M.P., Muscholl, E. & Pfeiffer, A. Muscarinic inhibition of potassium-induced noradrenaline release and its dependence on the calcium concentration. Naunyn-Schmiedeberg's Arch. Pharmacol. 291, 1–15 (1975). https://doi.org/10.1007/BF00510816
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00510816