Chemoselective regulation of TREK2 channel: activation by sulfonate chalcones and inhibition by sulfonamide chalcones.
Although it has not been extensively studied, a significant volume of literature suggests that TREK2 will probably turn out to be an important channel in charge of tuning neuronal transmitter and hormone levels. Thus, pharmacological tools which can manipulate this channel, such as selective agonists are essential both in drug design and to further our understanding of this system. Our investigations have shown that sulfonate ('O') chalcone and sulfonamide ('N') chalcones regulate the TREK2 channel in remarkably different ways: sulfonamide chalcone 5 behaved as an inhibitor with an IC(50) of 62 microM, whereas the sulfonate analogue 11 activated TREK2 with EC(50) value of 167 microM.
Kim
Eun-Jin
EJ
Medical Research Center for Neural Dysfunction, Department of Physiology, School of Medicine, Gyeongsang National University, Jinju 660-751, Republic of Korea.
Ryu
Hyung Won
HW
Curtis-Long
Marcus J
MJ
Han
Jaehee
J
Kim
Jun Young
JY
Cho
Jung Keun
JK
Kang
Dawon
D
Park
Ki Hun
KH
D002460:Cell Line; D047188:Chalcones / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D024683:Potassium Channels, Tandem Pore Domain / Q000187:drug effects*; D013449:Sulfonamides / Q000737:chemistry*; D013451:Sulfonic Acids / Q000737:chemistry*
D047188:Chalcones; C503438:KCNK10 protein, human; D024683:Potassium Channels, Tandem Pore Domain; D013449:Sulfonamides; D013451:Sulfonic Acids