Summary
Dog saphenous vein strips were perifused and exposed to seven concentrations of tyramine, ranging from 1.5 μM to 1.08 mM during 2.5 min. Fractional release of tritium (determined during and after the exposure to tyramine) was directly proportional to the concentration of tyramine. However, the percentage contribution by noradrenaline, normetanephrine and dihydroxymandelic acid to total release of radioactivity increased with tyramine concentration, whereas that by dihydroxyphenylglycol decreased. Inhibition of neuronal uptake by cocaine (8 μM) resulted in a marked reduction of the release of noradrenaline by tyramine, but did not affect the metabolic pattern of the released noradrenaline. In strips obtained from animals pretreated with reserpine and iproniazid and exposed to U-0521 and hydrocortisone, electrical stimulation caused no release of noradrenaline, but tyramine induced a small and transient efflux of noradrenaline. In another experimental series, strips obtained from untreated animals were subjected to electrical stimulation or tyramine during 40 min. Apart from differences in the metabolic pattern of noradrenaline released by either process, it was found that efflux due to tyramine was stable during the whole period of exposure, whereas noradrenaline release gradually and markedly decreased during the electrical stimulation period.
The results show that in this preparation tyramine releases noradrenaline by a mechanism which differs from that leading to the release by electrical stimulation, namely by a non-exocytotic mechanism, the transmitter being subject to oxidative deamination when diffusing through the axoplasm, before it reaches the synaptic gap.
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References
Brandão, F.: Inactivation of norepinephrine in an isolated vein. J. Pharmacol. Exp. Ther. 203, 23–29 (1977)
Brandão, F., Monteiro, J. G., Osswald, W.: Differences in the metabolic fate of noradrenaline released by electrical stimulation or by tyramine. Naunyn-Schmiedeberg's Arch. Pharmacol. 305, 37–40 (1978)
Graefe, K.-H., Stefano, F. J. E., Langer, S. Z.: Preferential metabolism of (−)-3H-norepinephrine through the deaminated glycol in the rat vas deferens. Biochem. Pharmacol. 22, 1147–1160 (1973)
Guimarães, S., Osswald, W.: Adrenergic receptors in the vein of the dog. Eur. J. Pharmacol. 5, 133–140 (1969)
Guimarães, S., Brandão, F., Paiva, M. Q.: A study of the adrenoceptor-mediated feedback mechanisms by using adrenaline as a false transmitter. Naunyn-Schmiedeberg's Arch. Pharmacol. 305, 185–188 (1978)
Kopin, I. J., Breek, G. R., Krauss, K. R., Weise, V. K.: Selective release of newly synthesized norepinephrine from the cat spleen during sympathetic nerve stimulation. J. Pharmacol. Exp. Ther. 161, 271–278 (1968)
Langer, S. Z.: Selective metabolic pathways for noradrenaline in the peripheral and in the central nervous system. Med. Biol. 52, 372–383 (1974)
Langer, S. Z., Enero, M. A.: The potentiation of responses to adrenergic nerve stimulation in the presence of cocaine: Its relationship to the metabolic fate of released norepinephrine. J. Pharmacol. Exp. Ther. 191, 431–443 (1974)
Leitz, F. H., Stefano, F. J. E.: The effect of tyramine, amphetamine and metaraminol on the metabolic disposition of 3H-norepinephrine released from the adrenergic neuron. J. Pharmacol. Exp. Ther. 178, 464–473 (1971)
Lindmar, R., Löffelholz, K.: The neuronal efflux of noradrenaline: Dependence on sodium and facilitation by ouabain. Naunyn-Schmiedeberg's Arch. Pharmacol. 284, 93–100 (1974)
Mekanontchai, R., Trendelenburg, U.: The neuronal and extraneuronal distribution of 3H-(−)-noradrenaline in the perfused rat heart. Naunyn-Schmiedeberg's Arch. Pharmacol. 308, 199–210 (1979)
Paton, D. M.: Mechanisms of efflux of noradrenaline from adrenergic nerves in rabbit atria. Br. J. Pharmacol. 49, 614–627 (1973a)
Paton, D. M.: Evidence for carrier-mediated efflux of noradrenaline from the axoplasm of adrenergic nerves in rabbit atria. J. Pharm. Pharmacol. 25, 265–267 (1973b)
Rodrigues-Pereira, E., Bönisch, H.: The uptake of tyramine and the release by tyramine of extravesicular noradrenaline in the isolated perfused hearts of reserpine pretreated rabbits. 3rd Meeting on Adrenergic Mechanisms, Porto, Abstracts, p. 19, 1978
Trendelenburg, U.: Classification of sympathomimetic amines. In: Handbook of experimental pharmacology (H. Blaschko and E. Muscholl, eds.), vol. 33, pp. 336–362. Berlin, Heidelberg, New York: Springer 1972
Trendelenburg, U.: Release induced by phenethylamines. In: The release of catecholamines from adrenergic neurons (D. M. Paton, ed.), pp. 333–354. Oxford, New York: Pergamon Press 1978
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Results presented in part to the 9th Annual Meeting of the Portuguese Pharmacological Society (Porto, December, 1978) Work supported by a grant from Instituto Nacional de Investigação Cientifica (FmP1)
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Brandão, F., Rodrigues-Pereira, E., Monteiro, J.G. et al. Characteristics of tyramine induced release of noradrenaline: Mode of action of tyramine and metabolic fate of the transmitter. Naunyn-Schmiedeberg's Arch. Pharmacol. 311, 9–15 (1980). https://doi.org/10.1007/BF00500297
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DOI: https://doi.org/10.1007/BF00500297