Mode of the ciguatoxin-induced supersensitivity in the guinea-pig vas deferens.
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.
D000818:Animals; D002922:Ciguatoxins / Q000494:pharmacology*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D008387:Marine Toxins / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D009469:Neuromuscular Junction / Q000187:drug effects; D009638:Norepinephrine / Q000378:metabolism; D011188:Potassium / Q000378:metabolism; D012110:Reserpine / Q000494:pharmacology; D012964:Sodium / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013779:Tetrodotoxin / Q000494:pharmacology; D014649:Vas Deferens / Q000187:drug effects
D008387:Marine Toxins; D002922:Ciguatoxins; D013779:Tetrodotoxin; D012110:Reserpine; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium; D009638:Norepinephrine