Mechanisms of the localized Ca2+ influx induced by mechanical stress in the presence of lysophosphatidic acid

• Published in: Japanese Journal of Pharmacology 2000, Vol.82 (suppl.1), p.145-145
• Main Authors: Maeyama, Naoto, Ohata, Hisayuki, Yamamoto, Masayuki, Momose, Kazutaka
• Format: Article
• Language: eng ; jpn
• ISSN: 0021-5198
• DOI: 10.1016/S0021-5198(19)48043-8

We have reported that localized Ca^2+ influx(Ca^2+ spots) occurred from a restricted region on the apical membrane of lens epithelial cells loaded with fluo-4 when the cells were stimulated mechanically in the presence of lysophosphatidic acid (LPA), that an intercellular phospholipid messenger. It is well known that LPA activates Rho-dependent signal transduction pathway leading to the formation of focal adhesion and stress fibers. In addition, it is suggested that integrin functions as mechanoreceptor. The aim of this study is to clarity the involvement of Rho-mediated signal transduction and integrin signaling in Ca^2+ spots in cultured lens epithelial cells. Pretreatment of Clostridium botulinum exoenzyme C3 transferase, an inhibitor of Rho protein, or cytochalasin D, which depolymerizes the actin cytoskeleton, blocked formation of stress fibers, but not affect the Ca^2+ spots. Additionally, genistein, an inhibitor of tyrosine kinase including pp125^FAK , did not inhibit the Ca^2+ spots. On the other hand, GRGDSP, an inhibitor of integrin, partially inhibited the Ca^2+ spots. These results suggest that LPA enhances the mechanical stress-induced Ca^2+ spots by modulating recognizing site of integrin to RGD sequence, but not by formation of stress fibers.