Transient receptor potential V2 expressed in sensory neurons is activated by probenecid.
Temperature-activated transient receptor potential ion channels (thermoTRPs) are known to function as ambient temperature sensors and are also involved in peripheral pain sensation. The thermoTRPs are activated by a variety of chemicals, of which specific activators have been utilized to explore the physiology of particular channels and sensory nerve subtypes. The use of capsaicin for TRPV1 is an exemplary case for nociceptor studies. In contrast, specific agents for another vanilloid subtype channel, TRPV2 have been lacking. Here, we show that probenecid is able to activate TRPV2 using electrophysiological and calcium imaging techniques with TRPV2-expressing HEK293T cells. Five other sensory thermoTRPs-TRPV1, TRPV3, TRPV4, TRPM8 and TRPA1-failed to show a response to this drug in the same heterologous expression system, suggesting that probenecid is a specific activator for TRPV2. Probenecid-evoked responses were also reproduced in a distinct subset of cultured trigeminal neurons that were responsive to 2-aminoethoxydiphenyl borate, a TRPV1-3 activator. The probenecid-sensitive neurons were mainly distributed in a medium to large-diameter population, in agreement with previous observations with TRPV2 immunolocalization. Under inflammation, probenecid elicited nociceptive behaviors in in vivo assays. These results suggest that TRPV2 is specifically activated by probenecid and that this chemical might be useful for investigation of pain-related TRPV2 function.
Bang
Sangsu
S
Korea University Graduate School of Medicine, Seoul 136-705, Republic of Korea.
Kim
Kyung Yoon
KY
Yoo
Sungjae
S
Lee
Sang-Heon
SH
Hwang
Sun Wook
SW
D000277:Adjuvants, Pharmaceutic / Q000494:pharmacology; D000818:Animals; D001896:Boron Compounds / Q000494:pharmacology; D015220:Calcium Channels / Q000235:genetics*; D002460:Cell Line; D048429:Cell Size; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D006801:Humans; D051379:Mice; D008813:Mice, Inbred ICR; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism*; D009619:Nociceptors / Q000187:drug effects / Q000378:metabolism*; D010146:Pain / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D018408:Patch-Clamp Techniques; D011339:Probenecid / Q000494:pharmacology*; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D050916:TRPV Cation Channels / Q000235:genetics*; D012668:Trigeminal Ganglion / Q000187:drug effects / Q000378:metabolism*
D000277:Adjuvants, Pharmaceutic; D001896:Boron Compounds; D015220:Calcium Channels; D012333:RNA, Messenger; D050916:TRPV Cation Channels; C485717:Trpv2 protein, mouse; C109986:2-aminoethoxydiphenyl borate; D011339:Probenecid