Mode of action of ciguatoxin from the Spanish Mackerel, Scomberomorus commersoni, on the guinea-pig ileum and vas deferens

Abstract

Ciguatoxin causes a sustained contraction of the guinea-pig ileum at all doses tested. The contraction was dose dependent and at a high dose of 0.25 mouse units/ml the contraction lasted for approximately 24 min. Associated with this sustained contraction were bursts of contractile activity. The ileum was refractory to repeated doses of ciguatoxin. The response to ciguatoxin was completely blocked by atropine, tetrodotoxin and low Na+ Ringer but was unaffected by hexamethonium or mepyramine. Ciguatoxin did not alter ileal responses to histamine, acetylcholine and 5-hydroxytryptamine. The ileal response to nicotine was, however, irreversibly reduced by prior exposure to ciguatoxin. Eserine potentiated the ileal response to ciguatoxin. It is proposed that the contractile action of ciguatoxin on the guinea-pig ileum is the result of a release of acetylcholine from cholinergic nerve terminals. This release is via nerve excitation produced by a Na+-dependent depolarization of postganglionic neural elements. The tachyphylactic nature of the action of ciguatoxin indicates that nerve stimulation is followed by nerve blockade, probably as the result of further nerve depolarization caused by ciguatoxin. The action of ciguatoxin isolated here is not different from the action of ciguatoxin isolated from moray eel viscera when tested on guinea-pig vas deferens. Ciguatoxin has a similar indirect action on the ileum and vas deferens. The action of ciguatoxin is compared with the action of other marine toxins on the guinea-pig ileum and vas deferens, particularly okadaick acid, a toxin chemically similar to ciguatoxin.