Mode of the ciguatoxin-induced supersensitivity in the guinea-pig vas deferens

Y Ohizumi, Y Ishida and S Shibata

Ciguatoxin (CTX; 10(-7) X 10(-7) g/ml), the most potent marine toxin isolated from a number of tropical and subtropical fishes, shifted the dose-contractile response curves for norepinephrine (NE) and K+ to the left in a parallel manner in the guinea-pig isolated vas deferens, indicating that CTX caused supersensitivity. The CTX-induced potentiation was inhibited or abolished in the presence of tetrodotoxin (5 X 10(-7) M) or saxitoxin (5 X 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/day, twice) almost completely prevented the release of NE by CTS, such pretreatment had no affect on the ability of CTX to potentiate responses to NE and K+. Furthermore, after cold storage (4 degrees C for 7 days) of tissues, the contractile response to NE (3 X 10(-6) M) and K+ (20 mM) was still profoundly potentiated after treatment with CTX (5 X 10(-7) g/ml). CTX (10(-7)-10(- 5) g/ml) by itself had no apparent effect on either Na+, K+-adenosine triphosphatase activity or Na+ content of the vas deferens. However, in the presence of ouabain, CTX elevated the Na content of the vas deferens treated with ouabain alone by 27%. This effect of CTX was abolished by tetrodotoxin. These data suggest that CTX causes an increasing Na+ permeability across the TTX sensitive Na+ channels of smooth muscle cell, and this may play an important role in its mechanism of potentiation.

Volume 221, Issue 3, pp. 748-752, 06/01/1982
Copyright © 1982 by American Society for Pharmacology and Experimental Therapeutics