title: Expression and function of bradykinin receptors in microglia.
abstract: Expression of bradykinin (BK) receptors and their cellular function were investigated in microglia. Microglial cells were isolated from mixed cultures of cerebrocortical cells from postnatal day 3 Wistar rats. Reverse transcription-PCR (RT-PCR) showed that rat primary microglia express mRNAs for the type 2 bradykinin (B(2)) receptor subtype but not the type 1 (B(1)) receptor subtype under our experimental condition. However, the expression of B(1) receptor was greatly up-regulated after the treatment of microglia with BK for 24 hours. The expression of B(2) receptor in microglia was further confirmed by immunocytochemistry. Membrane currents were measured using whole-cell recording under voltage-clamp conditions. In 14% of patched cells (12/85 cells), BK (100-200 nM) induced an outward current at the holding potential of -20 mV, with oscillations in 2 cases. The BK-induced outward current was transient and desensitized rapidly. TEA inhibited the BK-induced outward current in a dose-dependent manner. These results suggest that microglia express B(2) receptors and presumably increase the intracellular Ca(2+) concentration via inositol trisphosphate with the subsequent activation of Ca(2+)-dependent K(+) channels. Our data provide the first evidence that microglia express functional BK receptors and support the idea that microglia play an important role in CNS inflammatory responses.
authors.affiliation: Laboratory of Pathophysiology, Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, 812-8582, Fukuoka, Japan. noda@phar.kyushu-u.ac.jp
authors.forename: Mami
authors.initials: M
authors.lastname: Noda
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Kariura
authors.forename: Taiju
authors.initials: T
authors.lastname: Amano
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Manago
authors.forename: Kaori
authors.initials: K
authors.lastname: Nishikawa
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Aoki
authors.forename: Keiji
authors.initials: K
authors.lastname: Wada
mesh_terms: D000818:Animals; D001920:Bradykinin / Q000378:metabolism* / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects; D002478:Cells, Cultured; D017931:DNA Primers / Q000737:chemistry; D004983:Ethanolamines / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D017628:Microglia / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D017931:DNA Primers; D004983:Ethanolamines; D015221:Potassium Channels; D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin; C009546:triethanolamine; D001920:Bradykinin