Chronic bradykinin treatment alters 1α,25-dihydroxyvitamin D3-induced calcium current modulation in pre-osteoblasts.
Bradykinin (BK) is involved in bone resorption in chronic inflammatory diseases. During bone formation, 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) plays an important role in the regulation of Ca2+. In osteoblasts, 1,25(OH)2D3 stimulates transmembrane influx of Ca2+ through voltage-sensitive Ca2+ channels (VSCCs). Voltage sensitive Ca2+ channels serve as crucial mediators of membrane excitability and many Ca2+-dependent functions, including bone growth, regulation of proliferation, enzyme activity and gene expression. The purpose of this study was to investigate the effects of BK and 1,25(OH)2D3 on VSCC currents carried by Ba2+ (IBa). Application of 1,25(OH)2D3 facilitated IBa in a voltage-dependent manner. Pretreatment with SQ22536 (an adenylate cyclase inhibitor) attenuated 1,25(OH)2D3-induced facilitation of IBa. Bradykinin and BK1 receptor agonist [Lys-des-Arg9]-BK also facilitated IBa. After 24 h or 7 days exposure to BK, that is, under chronic inflammatory conditions, application of 1,25(OH)2D3 inhibited IBa. In addition, pretreatment with PD98,059, a mitogen-activated protein kinase (MAPK) tyrosine kinase inhibitor, attenuated 1,25(OH)2D3-induced inhibition of IBa. These results indicate that, under normal conditions, 1,25(OH)2D3 acts with adenylate cyclase to facilitate VSCCs, whereas under chronic inflammatory conditions it acts with MAPK to inhibit VSCCs in pre-osteoblasts.
Department of Orthodontics, Oral Health Science Center hrc7, Tokyo Dental College, 1-2-2 Masago, Mihama-ku, Chiba 261-8502, Japan.
Yushi
Y
Uchida
Takayuki
T
Endoh
Masakazu
M
Tazaki
Kenji
K
Sueishi
D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001464:Barium / Q000737:chemistry / Q000378:metabolism; D001862:Bone Resorption / Q000378:metabolism; D001920:Bradykinin / Q000008:administration & dosage*; D002117:Calcitriol / Q000008:administration & dosage*; D002118:Calcium / Q000378:metabolism*; D020864:Calcium Channels, N-Type / Q000378:metabolism*; D002460:Cell Line; D004789:Enzyme Activation / Q000187:drug effects*; D005419:Flavonoids / Q000494:pharmacology; D007249:Inflammation / Q000378:metabolism; D051379:Mice; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques
D000067956:Adenylyl Cyclase Inhibitors; D020864:Calcium Channels, N-Type; D005419:Flavonoids; D001464:Barium; D020929:Mitogen-Activated Protein Kinase Kinases; D000262:Adenylyl Cyclases; D002117:Calcitriol; D001920:Bradykinin; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; D002118:Calcium