Mode of the excitatory and inhibitory actions of ciguatoxin in the guinea-pig vas deferens

Abstract

Ciguatoxin (CTX), one of the most potent known toxic substances among marine toxins, causes a contraction in the isolated guinea-pig vas deferens at the concentration of above 3 x 10(-7) g/ml. The CTX-induced contraction of the vas deferens was inhibited or abolished by a treatment with phentolamine or guanethidine, but not affected in the presence of atropine or mecamylamine. Furthermore, this contraction was blocked by a treatment with tetrodotoxin, procaine or cold storage and incubation in a low Na+ medium. On the other hand, CTX markedly potentiated the contraction of vas deferens which was induced by norepinephrine (NE), acetylcholine or high-K, whereas it inhibited the contractile response to transmural stimulation. CTX caused a marked release of NE from the adrenergic nerves, which was blocked after treatment with tetrodotoxin or incubation in a Ca-free medium. On the basis of these results, it is suggested that the CTX-induced contraction is the result of an indirect action mediated through the NE release from the adrenergic nerve terminals and that the effect of NE released from the presynaptic sites is potentiated by CTX at the postsynaptic sites. The inhibitory effect of CTX on the contractile response to transmural stimulation may be due to decreasing the transmitter release caused by stimulation.