Blockade of colchicine-induced inhibition of vasopressin-stimulated osmotic water flow: failure to influence microtubule formation.
Colchicine inhibits vasopressin-induced osmotic water flow across isolated toad urinary bladder. Concomitantly, colchicine has been shown to reduce the relative cytoplasmic volume fraction of microtubules in the apical granular cells of this epithelium that have been shown previously to mediate the hydroosmotic effect of vasopressin. Therefore, an intact cytoskeleton has been postulated to be a requirement for a full response to vasopressin. Since it has been demonstrated recently that cyclooxygenase inhibitors (meclofenamic acid) abrogate the inhibition by colchicine of vasopressin-stimulated water flow, we tested by stereological criteria the hypothesis that colchicine in the presence of meclofenamic acid does not prevent the polymerization of tubulin. Our results show that the relative cytoplasmic volume fraction of microtubules was reduced 75% by colchicine in the presence or absence of meclofenamic acid. An alternative explanation of the inhibitory action of colchicine is its ability in the toad urinary bladder to enhance the endogenous synthesis of and sensitivity to prostaglandin E, a potent negative modulator of vasopressin-stimulated water flow. An intact microtubular component of the cytoskeleton does not appear to be required for a maximal response to a physiological dose of vasopressin.
D000818:Animals; D002024:Bufo marinus; D002463:Cell Membrane Permeability; D003078:Colchicine / Q000494:pharmacology*; D003599:Cytoskeleton / Q000187:drug effects*; D008469:Meclofenamic Acid / Q000494:pharmacology*; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism*; D009995:Osmosis; D011458:Prostaglandins E / Q000378:metabolism; D014404:Tubulin / Q000378:metabolism*; D001743:Urinary Bladder / Q000187:drug effects* / Q000378:metabolism; D014667:Vasopressins / Q000494:pharmacology*; D014882:Water-Electrolyte Balance / Q000187:drug effects; D062367:ortho-Aminobenzoates / Q000494:pharmacology*
D011458:Prostaglandins E; D014404:Tubulin; D062367:ortho-Aminobenzoates; D014667:Vasopressins; D008469:Meclofenamic Acid; D003078:Colchicine