Evidence for involvement of microtubules in the action of vasopressin in toad urinary bladder. I. Functional studies on the effects of antimitotic agents on the response to vasopressin.
The antimitotic agents colchicine, podophyllotoxin, and vinblastine inhibit the action of vasopressin and cyclic AMP on osmotic water movement in the toad urinary bladder. The alkaloids have no effect on either basal or vasopressin-stimulated sodium transport or urea flux across the tissue. Inhibition of vasopressin-induced water movement is half-maximal at the following alkaloid concentrations: colchicine, 1.8 X 10(-6) M; podophyllotoxin, 5 X 10(-7)M; and vinblastine, 1 X 10(-7)M. The characteristics of the specificity, time-dependence and temperature-dependence of the inhibitory effect of colchicine are similar to the characteristics of the interaction of this drug with tubulin in vitro, and they differ from those of its effect on nucleoside transport. Inhibition of the vasopressin response by colchicine, podophyllotoxin, and vinblastine is not readily reversed. The findings support the view that the inhibition of vasopressin-induced water movement by the antimitotic agents is due to the interaction of these agents with tubulin and consequent interference with microtubule integrity and function. Taken together with the results of biochemical and morphological studies, the findings provide evidence that cytoplasmic microtubules play a critical role in the action of vasopressin on transcellular water movement in the toad bladder.
D000818:Animals; D001692:Biological Transport; D002024:Bufo marinus; D003078:Colchicine / Q000494:pharmacology; D000242:Cyclic AMP / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D066298:In Vitro Techniques; D008870:Microtubules / Q000502:physiology*; D011034:Podophyllotoxin / Q000494:pharmacology; D001743:Urinary Bladder / Q000378:metabolism*; D014667:Vasopressins / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D014747:Vinblastine / Q000494:pharmacology; D014867:Water / Q000378:metabolism*
D014867:Water; D014667:Vasopressins; D014747:Vinblastine; D000242:Cyclic AMP; D011034:Podophyllotoxin; D003078:Colchicine