Inhibitory modulation of ATP-sensitive potassium channels by gallate-ester moiety of (-)-epigallocatechin-3-gallate.
(-)-Epigallocatechin-3-gallate (EGCG), a major polyphenolic substance found in green tea, is well recognized to be beneficial for human health. However, it is still controversial as to what dose of this compound is indeed good for human health. Though some recent studies have interestingly reported various beneficial effects of EGCG in cell culture system, however, plasma levels of EGCG attainable by oral regular intake in humans are normally in nanomolar range. However, potential side effects of EGCG when administered parenterally at higher concentration have not been thoroughly tested. Here, we evaluated the effect of EGCG on ATP-sensitive potassium (K(ATP)) channels expressed in Xenopus oocytes. EGCG inhibited the activity of the Kir6.2/SUR1 and Kir6.2DeltaC36 channels with IC(50) of 142+/-37 and 19.9+/-1.7microM, respectively. Inhibition of EGCG was also observed in Kir6.2/SUR2A or Kir6.2/SUR2B channels. Notably, (-)-epicatechin-3-gallate (ECG), another major polyphenolic substance in green tea, was found to reduce the channel activity with greater potency than EGCG. In contrast to EGCG and ECG, which have the gallic acid-ester moiety in their own structures, (-)-epigallocatechin and (-)-epicatechin exhibited very weak inhibition of the K(ATP) channel. Collectively, these results suggest that the gallate-ester moiety of epicatechins may be critical for inhibiting the K(ATP) channel activity via the pore-forming subunit Kir6.2 and this may be a possible mechanism by which green tea extracts or EGCG may cause unexpected side effects at micromolar plasma level.
Baek
Won-Ki
WK
Department of Microbiology, Keimyung University School of Medicine, Daegu 700-712, Republic of Korea.
Jang
Byeong-Churl
BC
Lim
Jun Hee
JH
Kwon
Taeg-Kyu
TK
Lee
Hyun-Young
HY
Cho
Chi-Heum
CH
Kim
Dae-Kwang
DK
Shin
Dong-Hoon
DH
Park
Jong-Gu
JG
Lim
Jeong-Geun
JG
Bae
Ji-Hyun
JH
Bae
Jae-Hoon
JH
Yoo
Sun Kyun
SK
Park
Won-Kyun
WK
Song
Dae-Kyu
DK
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D002392:Catechin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D015640:Ion Channel Gating / Q000187:drug effects; D007515:Islets of Langerhans / Q000166:cytology; D008564:Membrane Potentials / Q000187:drug effects; D015394:Molecular Structure; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism; D026902:Potassium Channel Blockers / Q000737:chemistry / Q000494:pharmacology*; D024661:Potassium Channels, Inwardly Rectifying / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D021122:Protein Subunits; D013329:Structure-Activity Relationship; D014982:Xenopus laevis; D000099161:Kcnj11 Channel
D000255:Adenosine Triphosphate; D002392:Catechin; D026902:Potassium Channel Blockers; D024661:Potassium Channels, Inwardly Rectifying; D021122:Protein Subunits; D000099161:Kcnj11 Channel; C045651:epigallocatechin gallate