title: Involvement of TRP channels in the signal transduction of bradykinin in human osteoblasts.
abstract: Bradykinin (BK), a mediator of pain and inflammation, is involved in bone metabolism. We have previously reported that BK increased the synthesis of interleukin-6 and prostaglandin E(2) via phosphorylation of ERK1/2 in human osteoblasts, SaM-1. In the present study, we investigated the signal transduction pathway of BK focusing on intracellular Ca(2+) kinetics in SaM-1 cells. Bath-applied BK increased intracellular Ca(2+) concentration through the activation of B(2) receptors. Removal of extracellular Ca(2+) attenuated the effects of BK. Additionally, thapsigargin, endoplasmic reticulum Ca(2+) pump inhibitor, completely inhibited BK-induced increase of intracellular Ca(2+). These results suggested that bath-applied BK activated store-operated Ca(2+) channels (SOCCs) following Ca(2+) store depletion via B(2) receptor. Although the molecular components of SOCCs have yet to be conclusively identified in all cell types, recent studies demonstrated that transient receptor potential canonical (TRPC) channels are candidates for them. TRPC1, TRPC3, TRPC4 and TRPC6 were expressed in SaM-1 cells and inhibitors of TRP channel, 2-aminoethoxydiphenyl borate, GdCl(3), LaCl(3) and flufenamic acid, inhibited the effects of BK. These findings suggested that BK activated SOCCs and induced Ca(2+) influx via B(2) receptor in human osteoblasts. Molecular components of the SOCCs are suggested to be TRPC channels.
authors.affiliation: Department of Pharmacology, School of Dentistry, Aichi-Gakuin University, 1-100 Kusumoto-cho, Chikusa-ku, Nagoya 464-8650, Japan. suzuyasu@dpc.aichi-gakuin.ac.jp
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kodama
authors.forename: Shigemi
authors.initials: S
authors.lastname: Goto
authors.forename: Akifumi
authors.initials: A
authors.lastname: Togari
mesh_terms: D001896:Boron Compounds / Q000494:pharmacology; D001920:Bradykinin / Q000494:pharmacology / Q000502:physiology*; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D005439:Flufenamic Acid / Q000494:pharmacology; D005682:Gadolinium / Q000494:pharmacology; D006801:Humans; D007811:Lanthanum / Q000494:pharmacology; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism*; D043782:Receptor, Bradykinin B2 / Q000819:agonists; D015398:Signal Transduction; D050052:TRPC Cation Channels / Q000378:metabolism*
chemical_list: D001896:Boron Compounds; D043782:Receptor, Bradykinin B2; D050052:TRPC Cation Channels; C028521:lanthanum chloride; D005439:Flufenamic Acid; D007811:Lanthanum; D005682:Gadolinium; C109986:2-aminoethoxydiphenyl borate; C038958:gadolinium chloride; D001920:Bradykinin; D002118:Calcium