Physiological and pharmacological role of lysophosphatidic acid as modulator in mechanotransduction

The mechanotransduction mechanism is believed to play an important role in maintenance of cellular homeostasis in a wide variety of cell types. In par ticular, the mechanotransduction system in vascular endothelial cells may b e an essential mechanism for local hemodynamic control. Elevations in intra cellular free Ca2+ concentration ([Ca2+](i)) are an important signal in the initial step of mechanotransduction and mechanosensitive (MS) cation chann els are thought to be a putative pathway; however, the molecular mechanisms remain unclear. We found that lysophosphatidic acid (LPA), a bioactive pho spholipid, sensitizes the response of [Ca2+](i) to mechanical stress in sev eral cell types. Employing real-time, confocal microscopy, local increases in [Ca2+](i) in several regions within the cell during application of mecha nical stress were clearly visualized in bovine Ions epithelial and endothel ial cells in the presence of LPA. The phenomenon was termed "Ca2+ spots". P harmacological studies revealed that Ca2+ spots arise due to influx through MS channels. In this report, our data indicating the possible significance of LPA as an endogenous factor involved in regulation of mechanotransducti on is reviewed. Furthermore, our findings suggest that the Ca2+ spot is a n ovel phenomenon occurring as an elementary. Ca-influx event through MS chan nels directly coupled with the initial step in mechanotransduction.