title: Activation properties of heterologously expressed mammalian TRPV2: evidence for species dependence.
abstract: TRPV2 has been proposed as a potential pain target, in part due to its relatedness to the nociceptor TRPV1 and to its reported activation by noxious high temperatures (>52 degrees C). However, TRPV2 responses to heat as well as to the nonselective agonist 2-aminoethoxydiphenyl borate (2-APB) have not been universally reproduced in other laboratories, leading to debate about the activation properties of this channel. Here, we report the expression of rat, mouse, and human TRPV2 in HEK293 cells and the differential properties of their responses to heat and 2-APB. Expression of mouse or rat TRPV2 in HEK293 cells resulted in robust channel activation when induced by either temperature (>53 degrees C) or 2-APB. By contrast, expression of human TRPV2 did not lead to detectable activation by either of these stimuli. Human TRPV2 protein was expressed at levels comparable with those of rat TRPV2, exhibited similar surface localization and responded to a novelly identified TRPV2 agonist, Delta(9)-tetrahydrocannabinol, indicating that human TRPV2 is functionally expressed on the cell surface. Studies using deletion mutants and chimeras between rat and human TRPV2 indicated that both amino- and carboxyl-cytoplasmic termini of rat TRPV2 are important for responses to heat and 2-APB but can be supplied in trans to form an active channel. The present study not only confirms and extends previous reports demonstrating that rat and mouse TRPV2 respond to 2-APB and noxious heat but also indicates that further investigation will be required to elucidate TRPV2 activation and regulatory mechanisms.
authors: Analgesics Team, East Coast Research and Early Development, Johnson & Johnson Pharmaceutical Research and Development, L.L.C., Spring House, Pennsylvania 19477-0776, USA.
authors: Michael P
authors: MP
authors: Neeper
authors: Yi
authors: Y
authors: Liu
authors: Tasha L
authors: TL
authors: Hutchinson
authors: Yan
authors: Y
authors: Wang
authors: Christopher M
authors: CM
authors: Flores
authors: Ning
authors: N
authors: Qin
mesh_terms: D000595:Amino Acid Sequence; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology; D000818:Animals; D001896:Boron Compounds / Q000494:pharmacology; D015220:Calcium Channels / Q000096:biosynthesis* / Q000235:genetics; D002460:Cell Line; D013759:Dronabinol / Q000494:pharmacology; D006358:Hot Temperature; D006801:Humans; D051379:Mice; D009619:Nociceptors / Q000378:metabolism; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D017384:Sequence Deletion; D013045:Species Specificity; D050916:TRPV Cation Channels / Q000819:agonists / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism
chemical_list: D018712:Analgesics, Non-Narcotic; D001896:Boron Compounds; D015220:Calcium Channels; D011993:Recombinant Fusion Proteins; D050916:TRPV Cation Channels; C494482:TRPV1 protein, human; C493921:TRPV1 protein, mouse; C400769:TRPV2 protein, human; C493922:Trpv1 protein, rat; C485717:Trpv2 protein, mouse; C476722:Trpv2 protein, rat; D013759:Dronabinol; C109986:2-aminoethoxydiphenyl borate