Mechanism of the excitatory action of palytoxin and N-acetylpalytoxin in the isolated guinea-pig vas deferens.

Palytoxin (PTX), one of the most well known potent toxic substances among marine toxins, caused a slow phasic contraction of the isolated guinea-pig vas deferens (second component) followed by the first rapid phasic contraction (first component) at concentrations above 3 x 10(-9) M. N-acetylpalytoxin, one of its derivatives, also produced similar actions but its potency was about 1/100 of that of PTX. The second component of PTX-induced contraction, but not the first component, was markedly inhibited by treatments with phentolamine, reserpine and 6-hydroxydopamine, but remained unaffected by atropine and mecamylamine pretreatment. Tetrodotoxin partially inhibited the second component, whereas the second component was markedly inhibited by solutions low in Na+ (85.2 mM) or containing verapamil (10(-6) M). Both components were completely abolished by high Mg++ or Ca++-free medium. It is concluded that the first component was the result of a direct action of PTX on smooth muscle sites, whereas the second phase was the result of an indirect action mediated through the norephinephrine release from the adrenergic nerve terminals.