Glibenclamideのマクロファージにおけるコレステロールエステル合成能におよぼす影響

Abstract

To clarify the process of atherosclerosis, the mechanism of cholesteryl ester accumulation in macrophages must be elucidated. Many drugs, hormones and cytokines are known to affect this process. Glibenclamide is widely used for the treatment of diabetes mellitus. However, the effects of this drug on cholesterol metabolism are not well known. In this study, we examined the effect of glibenclamide on cholesteryl ester synthesis and cellular cholesterol contents in macrophages. Glibenclamide enhanced cholesteryl ester synthesis in a concentrationdependent manner. This effect was observed both in the presence and absence of LDL. Degradation and association of 125I-LDL were not changed by glibenclamide. However, glibenclamide inhibited cholesteryl ester accumulation. These findings suggest that glibenclamide did not change the metabolism of LDL and that cholesteryl ester hydrolysis and efflux may be enhanced by glibenclamide. To study the involvement of ATP-sensitive potassium channel in the action of glibenclamide, the effect of lemakalim and nicorandil, potassium channel openers, on cholesteryl ester synthesis was examined. Neither nicorandil nor lemakalim had any effects on cellular cholesteryl ester synthesis. In addition, nicorandil did not alleviate the action of glibenclamide. These findings suggest that a factor other than the ATP-sensitive potassium channel is involved in the inhibition of cholesteryl ester accumulation by glibenclamide.