2-aminoethoxydiphenyl borate is a common activator of TRPV1, TRPV2, and TRPV3.
The transient receptor potential (TRP) superfamily contains a large number of proteins encoding cation permeable channels that are further divided into TRPC (canonical), TRPM (melastatin), and TRPV (vanilloid) subfamilies. Among the six TRPV members, TRPV1, TRPV2, TRPV3, and TRPV4 form heat-activated cation channels, which serve diverse functions ranging from nociception to osmolality regulation. Although chemical activators for TRPV1 and TRPV4 are well documented, those for TRPV2 and TRPV3 are lacking. Here we show that in the absence of other stimuli, 2-aminoethoxydiphenyl borate (2APB) activates TRPV1, TRPV2, and TRPV3, but not TRPV4, TRPV5, and TRPV6 expressed in HEK293 cells. In contrast, 2APB inhibits the activity of TRPC6 and TRPM8 evoked by 1-oleolyl-2-acetyl-sn-glycerol and menthol, respectively. In addition, low levels of 2APB strongly potentiate the effect of capsaicin, protons, and heat on TRPV1 as well as that of heat on TRPV3 expressed in Xenopus oocytes. In dorsal root ganglia neurons, supra-additive stimulations were evoked by 2APB and capsaicin or 2APB and acid. Our data suggest the existence of a common activation mechanism for TRPV1, TRPV2, and TRPV3 that may serve as a therapeutic target for pain management and treatment for diseases caused by hypersensitivity and temperature misregulation.
Hu
Hong-Zhen
HZ
Department of Physiology and Cell Biology, The Ohio State University, Columbus Ohio 43210, USA.
Gu
Qihai
Q
Wang
Chunbo
C
Colton
Craig K
CK
Tang
Jisen
J
Kinoshita-Kawada
Mariko
M
Lee
Lu-Yuan
LY
Wood
Jackie D
JD
Zhu
Michael X
MX
D000818:Animals; D001896:Boron Compounds / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000187:drug effects*; D002211:Capsaicin / Q000494:pharmacology*; D027682:Cation Transport Proteins / Q000819:agonists*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005727:Ganglia, Spinal / Q000378:metabolism; D006801:Humans; D007473:Ion Channels / Q000819:agonists*; D051379:Mice; D009474:Neurons / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects*; D050916:TRPV Cation Channels; D013696:Temperature; D014981:Xenopus
D001896:Boron Compounds; D015220:Calcium Channels; D027682:Cation Transport Proteins; D007473:Ion Channels; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; C485717:Trpv2 protein, mouse; C486760:Trpv3 protein, mouse; C109986:2-aminoethoxydiphenyl borate; D002211:Capsaicin; D002118:Calcium