Characteristics of tyramine induced release of noradrenaline: Mode of action of tyramine and metabolic fate of the transmitter

Summary Dog saphenous vein strips were perifused and exposed to seven concentrations of tyramine, ranging from 1.5 M 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 M) 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.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)