Curcumin inhibits bTREK-1 K+ channels and stimulates cortisol secretion from adrenocortical cells

被引:27
作者
Enyeart, Judith A. [1 ]
Liu, Haiyan [1 ]
Enyeart, John J. [1 ]
机构
[1] Ohio State Univ, Coll Med & Publ Hlth, Dept Neurosci, Columbus, OH 43210 USA
关键词
curcumin; TREK-1; ion channel; cortisol; adrenal;
D O I
10.1016/j.bbrc.2008.04.001
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Bovine adrenal zona fasciculata (AZF) cells express bTREK-1 K(+) channels that set the resting membrane potential. Inhibition of these channels by adrenocorticotropic hormone (ACTH) is coupled to membrane depolarization and cortisol secretion. Curcumin, a phytochemical with medicinal properties extracted from the spice turmeric, was found to modulate both bTREK-1 K(+) currents and cortisol secretion from AZF cells. In whole-cell patch clamp experiments, curcurmin inhibited bTREK-1 with an IC(50) of 0.93 mu M by a mechanism that was voltage-independent. bTREK-1 inhibition by curcumin occurred through interaction with an external binding site and was independent of ATP hydrolysis. Curcumin produced a concentration-dependent increase in cortisol secretion that persisted for up to 24 h. At a maximally effective concentration of 50 mu M curcumin increased secretion as much as 10-fold. These results demonstrate that curcumin potently inhibits bTREK-1 K(+) channels and stimulates cortisol secretion from bovine AZF cells. The inhibition of bTREK-1 by curcumin may be linked to cortisol secretion through membrane depolarization. Since TREK-1 is widely expressed in a variety of cells, it is likely that some of the biological actions of curcumin, including its therapeutic effects, may be mediated through inhibition of these K(+) channels. (c) 2008 Elsevier Inc. All rights reserved.
引用
收藏
页码:623 / 628
页数:6
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