Uncoupling by (−)-epigallocatechin-3-gallate of ATP-sensitive potassium channels from phosphatidylinositol polyphosphates and ATP
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- 作者：Jun-Yup Jin ; Sung-Hee Park ; Jae-Hoon Bae ; Ho-Chan Cho ; Jeong-Geun Lim ; Won Sun Park ; Jin Han ; Jin Ho Lee ; Dae-Kyu Song
- 关键词：Epicatechin ; ATP-sensitive potassium channel ; Phosphatidylinositol polyphosphate ; Insulin secretion ; Cardiomyocyte
- 刊名：Pharmacological Research
- 出版年：2007
- 出版时间：September 2007
- 年：2007
- 卷：56
- 期：3
- 页码：237-247
- 全文大小：1186 K
文摘
Of green tea catechins, (−)-epigallocatechin-3-gallate (EGCG) and (−)-epicatechin-3-gallate (ECG), but not (−)-epicatechin and (−)-epigallocatechin, inhibit the activity of ATP-sensitive potassium (KATP) channels at tens of micromolar concentrations, ECG being three times more effective than EGCG. Further, we found that by using cloned beta cell-type KATP channels, only EGCG at 1 μM, a readily achievable plasma concentration by oral intake in humans, but not other epicatechins, significantly blocked channel reactivation after ATP wash-out, suggesting that interaction of phosphatidylinositol polyphosphates (PIP) with the channel was impaired by EGCG. In addition, a 10-fold higher concentration of EGCG reduced the channel sensitivity to ATP, but not AMP and ADP. This effect of EGCG was greater in the channel with the sulfonylurea receptor (SUR) than with the inwardly rectifying K+ channel (Kir6.2) alone. Neomycin, a polycation, profoundly suppressed the effect of EGCG. Expectedly, glucose-stimulated cytosolic Ca2+ elevation in rat pancreatic beta cells, and insulin secretory responses to high glucose loading in vivo were impaired by EGCG. In rabbit cardiac myocytes, dinitrophenol-induced opening of the channel was delayed by 1 μM EGCG. These results suggest that EGCG may interact with PIP-binding sites on the Kir6.2 subunit. SUR further endows EGCG with an ability to interfere with an interaction of the γ-phosphate tail of ATP with Kir6.2. The specificity of EGCG possibly implies that 5′-OH of the B-ring on the pyrogallol moiety in the EGCG molecule may be critical for these actions of EGCG on the KATP channel.