MODE OF THE CIGUATOXIN-INDUCED SUPER-SENSITIVITY IN THE GUINEA-PIG VAS-DEFERENS

Abstract

Ciguatoxin (CTX; 10-7-5 .times. 10-7 g/ml), the most potent marine toxin isolated from a number of tropical and subtropical fish, shifted the dose-contractile response curves for norepinephrine (NE) and K+ to the left in a parallel manner in the quinea pig isolated vas deferens, indicating that CTX caused supersensitivity. The CTX-induced potentiation was inhibited or abolished in the presence of tetrodotoxin (5 .times. 10-7 M) or saxitoxin (5 .times. 10-7 M) and in Na+-deficient medium, but was not affected by phentolamine (10-6 M) and verapamil (10-6 M). Treatment with reserpine (2 mg/kg per day, twice) almost completely prevented the release of NE by CTX; such pretreatment had no affect on the ability of CTX to potentiate responses to NE and K+. After cold storage (4.degree. C for 7 days) of tissues, the contractile response to NE (3 .times. 10-6 M) and K+ (20 mM) was still profoundly potentiated after treatment with CTX (5 .times. 10-7 g/ml). CTX (10-7-10-5 g/ml) by itself had no apparent effect on Na+,K+-ATPase activity or Na+ content of the vas deferens. In the presence of ouabain, CTX elevated the Na content of the was deferens treated with ouabain alone by 27%. This effect of CTX was abolished by tetrodotoxin (TTX). CTX caused an increased Na+ permeability across the TTX-sensitive Na+ channels of smooth muscle cell and this may play an important role in its mechanism of potentiation.