5-hydroxytryptamine and neurotransmitter release in canine blood vessels. Inhibition by low and augmentation by high concentrations.

Abstract

3H] and mounted for supervision and isometric tension recording. The superfusate was collected for estimation of total radioactivity and for column chromatographic separation of norepinephrine[73 H] and its metabolites. 5Hydroxytryptamine (5-HT), 10 8 M and 10~ 7 M, inhibited the increase in smooth muscle tension and the release of norepinephrine|73 H] caused by transmural electric stimulation of the sympathetic nerve endings. By contrast, the increase in tension caused by direct stimulation of the smooth muscle with norepinephrine was either unchanged or augmented. In addition, 5-HT augmented the increase in tension with tyramine but did not affect the release of radiolabeled compounds by this substance. In unstimulated preparations low concentrations of 5-HT (10~ 7 M) caused contraction but did not affect the release of norepinephrine[73 H]. With a higher concentration (10~ 5 M) the release of neurotransmitter was markedly increased. This response was inhibited by cocaine. Whereas 5-HT-induced contractions were inhibited by phentolamine and methysergide, these antagonists had no effect on its inhibitory action at the sympathetic nerve ending. Hence, low concentrations of 5-HT depress sympathetic tone by inhibiting the release of transmitter during nerve depolarization. At higher concentrations 5-HT has a direct excitatory effect on vascular smooth muscle together with an indirect effect which involves the uptake of 5-HT into the sympathetic nerve ending via the cocaine-sensitive mechanism and the release of norepinephrine.