Intercellular Ca2+ Response Triggered by IP3 among Endothelial Cells in Shear Stress Flow

Abstract

A phenomenon has been observed in which intracellular Ca 2+ concentration in endothelial cells increases upon application of shear stress (Ca 2+ response). It is therefore assumed that Ca 2+ is the second messenger in the transfer of shear stress stimulation into cells. The Ca 2+ response is also known to spread to surrounding cells (Ca 2+ wave). We investigated the effects on Ca 2+ wave among cultured bovine aorta endothelial cells (BAECs) upon inhibiting the main intercellular signaling pathways, such as gap junction and paracrine pathways by inducing Ca 2+ wave using D-myo-inositol 1,4,5-trisphosphate, P4( 5)-(1-(2-nitrophenyl)ethyl) ester trisodium salt (Caged IP 3 ) due to an intracellular IP 3 elevation. In addition, we investigated the Ca 2+ wave among BAECs under shear stress loading. Using Caged IP 3 , local release of ATP from BAEC induced Ca 2+ wave. The Ca 2+ wave was inhibited by the inhibitors of paracrine pathways. Furthermore, the Ca 2+ response spread in the direction of the downstream under shear flow. These results suggest that paracrine pathway is dominant in both of flow and no flow conditions.