title: Involvement of TRPV2 activation in intestinal movement through nitric oxide production in mice.
abstract: Transient receptor potential channel vanilloid 2 (TRPV2) can detect various stimuli such as temperature (>52 °C), stretch, and chemicals, including 2-aminoethoxydiphenyl borate, probenecid, and lysophospholipids. Although expressed in many tissues, including sensory and motor neurons, TRPV2 expression and function in the gastrointestinal tract is poorly understood. Here, we show TRPV2 expression in the murine intestine and its involvement in intestinal function. Almost all mouse intestinal intrinsic sensory and inhibitory motor neurons, both cell bodies and nerve fibers, showed TRPV2 immunoreactivity. Several known TRPV2 activators increased cytosolic Ca²+ concentrations and evoked TRPV2-like current responses in dissociated myenteric neurons. Interestingly, mechanical stimuli activated inward currents in a strength-dependent manner, which were inhibited by a TRPV2 inhibitor tranilast. TRPV2 activation in isolated intestine inhibited spontaneous circular muscle contraction, which did not occur in the presence of the TRPV2 antagonist, tetrodotoxin or nitro oxide (NO) synthase pathway inhibitors. Also, increased intestinal NO production was observed in response to a TRPV2 agonist, and gastrointestinal transit in vivo was accelerated by TRPV2 agonists or an NO donor. In conclusion, TRPV2 may contribute to intestinal motility through NO production, and TRPV2 is a promising target for controlling intestinal movement.
authors.affiliation: Division of Cell Signaling, Okazaki Institute for Integrative Bioscience (National Institute for Physiological Sciences), National Institutes of Natural Sciences, Okazaki 444-8787, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Mihara
authors.forename: Ammar
authors.initials: A
authors.lastname: Boudaka
authors.forename: Koji
authors.initials: K
authors.lastname: Shibasaki
authors.forename: Akihiro
authors.initials: A
authors.lastname: Yamanaka
authors.forename: Toshiro
authors.initials: T
authors.lastname: Sugiyama
authors.forename: Makoto
authors.initials: M
authors.lastname: Tominaga
mesh_terms: D000818:Animals; D001896:Boron Compounds / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D002795:Choline O-Acetyltransferase / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D018274:Electroporation / Q000379:methods; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005769:Gastrointestinal Motility / Q000187:drug effects / Q000502:physiology*; D005786:Gene Expression Regulation / Q000187:drug effects; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D066298:In Vitro Techniques; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009197:Myenteric Plexus / Q000166:cytology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology; D018408:Patch-Clamp Techniques / Q000379:methods; D011339:Probenecid / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D043222:Ubiquitin Thiolesterase / Q000235:genetics / Q000378:metabolism
chemical_list: D001896:Boron Compounds; D015220:Calcium Channels; D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; D009419:Nerve Tissue Proteins; D020030:Nitric Oxide Donors; D012333:RNA, Messenger; D050916:TRPV Cation Channels; C485717:Trpv2 protein, mouse; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D009599:Nitroprusside; D009569:Nitric Oxide; C109986:2-aminoethoxydiphenyl borate; D052248:Nitric Oxide Synthase Type I; D002795:Choline O-Acetyltransferase; C489034:UCHL1 protein, rat; D043222:Ubiquitin Thiolesterase; D011339:Probenecid; D002118:Calcium; D019331:NG-Nitroarginine Methyl Ester