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 Ca2+ kinetics in SaM-1 cells. Bath-applied BK increased intracellular Ca2+ concentration through the activation of B-2 receptors. Removal of extracellular Ca2+ attenuated the effects of BK. Additionally, thapsigargin, endoplasmic reticulum Ca2+ pump inhibitor, completely inhibited BK-induced increase of intracellular Ca2+. These results suggested that bath-applied BK activated store-operated Ca2+ channels (SOCCs) following Ca2+ 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, GdCl3, LaCl3 and flufenamic acid, inhibited the effects of BK. These findings suggested that BK activated SOCCs and induced Ca2+ influx via B-2 receptor in human osteoblasts. Molecular components of the SOCCs are suggested to be TRPC channels. (C) 2011 Elsevier Inc. All rights reserved.