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

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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 chromaffín cells and compare these with corresponding actions of β-lumicolchicine. β-Lumicolchicine is a structural isomer of colchicine which neither binds microtubular protein (tubulin) nor interferes with microtubule assembly. Both colchicine and β-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+, β-lumicolchicine also inhibits K+-induced secretion. Because colchicine and β-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 β-lumicolchicine on K+-evoked secretion suggests different modes of action of these structural isomers on chromaffin cell function.