Direct and indirect actions of 5-hydroxytryptamine on the rat isolated vas deferens

The contractile effect of 5-hydroxytryptamine on the rat isolated vas deferens was analyzed. In tissues from reserpine-pretreated animals 5-hydroxytryptamine (1 X 10(-6) M-3 X 10(-4) M) induced effects which were much lower than those induced in tissues from normal animals; the effects of low and medium concentrations of 5-hydroxytryptamine were antagonized by methysergide, those of medium and high concentrations were inhibited by phentolamine. In tissues from normal animals 5-hydroxytryptamine-induced contractions were compared with those induced by noradrenaline. 5-Hydroxytryptamine was less potent than noradrenaline and exhibited tachyphylaxis when the time interval between two successive exposures was too short. Phentolamine and dihydroergocristine reduced the effects of 5-hydroxytryptamine at concentrations lower than those necessary to antagonize noradrenaline-induced effects. Methysergide only reduced the effects of lower concentrations of 5-hydroxytryptamine. Cross-protection experiments showed that when noradrenaline was added before dibenamine, responses to both 5-hydroxytryptamine and noradrenaline were maintained to a very similar degree, while when 5-hydroxytryptamine was used as a protecting agent only a small degree of protection was found both towards noradrenaline and 5-hydroxytryptamine-induced effects. Cocaine potentiated the effects of low concentrations of 5-hydroxytryptamine while inhibiting those of high concentrations. The present study provides direct and indirect evidences that the contractile effect of 5-hydroxytryptamine on the rat vas deferens is prevailingly due to the release of noradrenaline; in the lower part of the concentration-response curve also direct effects are involved which are mediated by an interaction with both tryptaminergic "D" receptors and alpha 1-adrenoceptors.