Mechanism of mesoconitine-induced contractile response in guinea pig vas deferens

Mesaconitine (MA) caused contraction of the isolated guinea pig vas deferens in a dose-dependent manner (3 × 10^-6-10^-4 g/ml) and nonspecifically potentiated the contractile response to norepinephrine (NE), acetylcholine, histamine and tyramine. Tachyphylaxis developed during the repeated application of MA. The contraction produced by MA was prevented by treatment with phentolamine, phenoxybenzamine, procaine, bretylium or tetrodotoxin, pretreatment with reserpine or 6-hydroxydopamine, or denervation. Atropine or hexamethonium did not abolish the effect of MA, excluding the possibility that the muscarinic and nicotinic receptors are the site of action of MA. MA elicited a dose-dependent release of NE from the isolated vas deferens which had been blocked by treatment with tetrodotoxin, pretreatment with reserpine, or the exclusion of calcium ion from the bath medium. Consequently, it is concluded that MA-induced contraction was brought about by the release of NE from pre-synaptic neuronal sites and by excitation of the post-synaptic membrane.