Comparison of the effects of colchicine and beta-lumicolchicine on cultured adrenal chromaffin cells: lack of evidence for an action of colchicine on receptor-associated microtubules.

Abstract

The involvement of microtubules in adrenomedullary secretion is presently unclear. Evidence exists for a possible role of microtubules in cholinergic nicotinic receptor-related events. We now describe the actions of the microtubule disrupter, colchicine, on primary cultures of bovine adrenal chromaffin cells and compare these with corresponding actions of beta-lumicolchicine. beta-Lumicolchicine is a structural isomer of colchicine which neither binds microtubular protein (tubulin) nor interferes with microtubule assembly. Both colchicine and beta-lumicolchicine were found to inhibit acetylcholine-induced secretion with similar potencies (half maximal inhibitory concentration 0.2-0.5 mM). The inhibitory actions of both drugs are time-dependent and reversible. However, unlike colchicine which has no inhibitory effects on secretion evoked by depolarization with excess K+, beta-lumicolchicine also inhibits K+-induced secretion. Because colchicine and beta-lumicolchicine have similar effects, the selective inhibitory actions of colchicine on nicotinic receptor-mediated secretion cannot in itself be used as evidence in support of a role of microtubules in receptor-mediated events. However, our data do not preclude such a role. Differences in the effect of colchicine and beta-lumicolchicine on K+-evoked secretion suggests different modes of action of these structural isomers on chromaffin cell function.