Chronic bradykinin treatment alters 1α,25-dihydroxyvitamin D₃-induced calcium current modulation in pre-osteoblasts
2012
Uchida, Yushi | Endoh, Takayuki | Tazaki, Masakazu | Sueishi, Kenji
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 24h or 7days 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.
Afficher plus [+] Moins [-]Mots clés AGROVOC
Informations bibliographiques
Cette notice bibliographique a été fournie par National Agricultural Library
Découvrez la collection de ce fournisseur de données dans AGRIS