AJP - Renal Physiology, Vol 249, Issue 4 464-F469, Copyright © 1985 by American Physiological Society
Blockade of colchicine-induced inhibition of vasopressin-stimulated osmotic water flow: failure to influence microtubule formation
D. A. Baron, R. M. Burch, P. V. Halushka and S. S. Spicer
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.
