Inhibition of microtubule polymerization by SK&F 96365, a blocker of receptor-linked Ca2+ entry.
SK&F 96365 (1-[beta-[3-(4-methoxyphenyl)propoxyl]-4-methoxyphenethyl]-1H-imid azole 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.
Mitsui-Saito
M
M
Department of Pharmaceutical Molecular Biology, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
Nakahata
N
N
Ohizumi
Y
Y
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002417:Cattle; D007093:Imidazoles / Q000494:pharmacology*; D008868:Microtubule Proteins / Q000378:metabolism*; D008870:Microtubules / Q000187:drug effects* / Q000378:metabolism; D011108:Polymers / Q000378:metabolism; D014747:Vinblastine / Q000494:pharmacology
D002121:Calcium Channel Blockers; D007093:Imidazoles; D008868:Microtubule Proteins; D011108:Polymers; D014747:Vinblastine; C063159:1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole