Summary
-
1.
Anaesthetized rabbits were infused for 20 min with 85 μg · kg−1 · min−1 (±)-α-methyladrenaline. The hearts dissected 15 min after the infusion contained 1.49 μg/g α-methyladrenaline; the endogenous noradrenaline content was correspondingly decreased.
-
2.
Hearts from α-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 α-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 show 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 α-methyladrenaline to noradrenaline occurring in the perfusate during administration of tyramine reflects the relative concentrations of the amines in the axoplasm.
Similar content being viewed by others
References
Barlow, R. B., Franks, F.: Specificity of some ganglion stimulants. Brit. J. Pharmacol. 42, 137–142 (1971)
Bogdanski, D. F., Brodie, B. B.: The effects of inorganic ions on the storage and uptake of H3-norepinephrine by rat hearts slices. J. Pharmacol. exp. Ther. 165, 181–189 (1969)
Chubb, I. W., De Potter, W. P., De Schaepdryver, A. F.: Tyramine does not release noradrenaline from splenic nerve by exocytosis. Naunyn-Schmiedeberg's Arch. Pharmacol. 274, 281–286 (1972)
Douglas, W. W.: The first Gaddum memorial lecture. Stimulus-secretion coupling: the concept and clues from chromaffin and other cells. Brit. J. Pharmacol. 34, 451–474 (1968)
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)
Dunnett, C. W.: A multiple comparison procedure for comparing several treatments with a control. J. Amer. statist. Ass. 50, 1096–1121 (1955)
Fozard, J. R., Muscholl, E.: A useful muscarinic parameter and the differential recording of atrial and ventricular tension in the perfused rabbit heart. Naunyn-Schmiedebergs Arch. Pharmak. 270, 319–325 (1971)
Fuder, H.: Der Einfluß von Calcium-Entzug und Methacholin auf die Freisetzung des falschen Überträgerstoffes α-Methyladrenalin aus dem isolierten Kaninchenherzen durch sympathische Nervenreizung und eine nicotinartige Substanz. Med. Inaug.-Diss., Mainz 1976
Garcia, A. G., Kirpekar, S. M.: Release of noradrenaline from the cat spleen by sodium deprivation. Brit. J. Pharmacol. 47, 729–747 (1973)
Garcia, A. G., Kirpekar, S. M.: On the mechanism of release of norepinephrine from cat spleen slices by sodium deprivation and calcium pretreatment. J. Pharmacol. exp. Ther. 192, 343–350 (1975)
Geffen, L. B., Livett, B. G., Rush, R. A.: Immunohistochemical localization of chromogranins in sheep sympathetic neurones and their release by nerve impulses, pp. 58–72. In: New Aspects of Storage and Release Mechanisms of Catecholamines (H. J. Schümann and G. Kroneberg, eds.). Berlin-Heidelberg-New York Springer 1970
Gewirtz, G. P., Kopin, I. J.: Release of dopamine-β-hydroxylase with norepinephrine during cat splenic nerve stimulation. Nature (Lond.) 227, 406–407 (1970)
Huković, S., Muscholl, E.: Die Noradrenalin-Abgabe aus dem isolierten Kaninchenherzen bei sympathischer Nervenreizung und ihre pharmakologische Beeinflussung. Naunyn-Schmiedebergs Arch. exp. Path. Pharmak. 244, 81–96 (1962)
Lindmar, R., Muscholl, E., Sprenger, E.: Funktionelle Bedeutung der Freisetzung von Dihydroxyephedrin und Dihydroxypseudo-ephedrin als “falschen” sympathischen Überträgerstoffen am Herzen. Naunyn-Schmiedebergs Arch. Pharmak. exp. Path. 256, 1–25 (1967)
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)
Muscholl, E.: Release of catecholamines from the heart, pp. 247–260. In: Mechanisms of Release of Biogenic Amines (U. S. von Euler, S. Rosell, and B. Uvnäs, eds.). Oxford: Pergamon Press 1966
Muscholl, E.: Adrenergic false transmitters. Handbook exp. Pharmacol. vol. 33 (H. Blaschko and E. Muscholl, eds.), pp. 618–660. Berlin-Heidelberg-New York: Springer 1972
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
Sachs, L.: Statistische Auswertungsmethoden. 3. Aufl., pp. 227–228. Berlin-Heidelberg-New York Springer 1972
Smith, A. D., De Potter, W. P., Moerman, E. H., De Schaepdryver, A. F.: Release of dopamine β-hydroxylase and chromogranin A upon stimulation of the splenic nerve. Tissue and Cell 2, 547–568 (1970)
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. Berlin-Heidelberg-New York: Springer 1972
Vanhoutte, P. M., Lorenz, R. R., Tyce, G. M.: Inhibition of norepinephrine-3H release from sympathetic nerve endings in veins by acetylcholine. J. Pharmacol. exp. Ther. 185, 386–394 (1973)
Wegwart, R.: Der Einfluß von Calcium-Entzug und Methacholin auf die Freisetzung des “falschen” Transmitters α-Methyladrenaline und endogenem Noradrenalin aus dem isolierten Kaninchenherzen durch Tyramin und Kalium. Med. Inaug.-Diss., Mainz 1976
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Fuder, H., Muscholl, E. & Wegwart, R. The effects of methacholine and calcium deprivation on the release of the false transmitter, α-methyladrenaline, from the isolated rabbit heart. Naunyn-Schmiedeberg's Arch. Pharmacol. 293, 225–234 (1976). https://doi.org/10.1007/BF00507345
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00507345