Inhibition of Microtubule Polymerization by SK&F 96365, a Blocker of Receptor-Linked Ca2+ Entry

SK&F 96365 (l-{β-[3-(4-methoxyphenyl)propoxyl]-4-methoxyphenethyl}-lH-imidazole hydrochloride) is widely used as an effective inhibitor of receptor-linked and capacitative Ca2+ entry. Since this inhibitor has additional effects such as inhibition of voltage-dependent Ca2+ channels, sarco- and endoplasmic reticula Ca2+ pumps and cell proliferation, its molecular mechanism of action remains to be solved. In the present study, we have investigated the effect of SK&F 96365 on microtubule protein isolated from bovine brain in vitro. SK&F 96365 depolymerized the polymerized microtubules in a concentration-dependent manner. This result suggests that SK&F 96365 directly depolymerizes microtubules, an effect that may contribute to the various actions of this compound.