Bradykinin-induced Ca(2+)-influx into cultured aortic endothelial cells is not regulated by inositol 1,4,5-trisphosphate or inositol 1,3,4,5-tetrakisphosphate.

Abstract

Since inositol 1,4,5-trisphosphate (1,4,5-IP3) and inositol 1,3,4,5-tetrakisphosphate (1,3,4,5-IP4) have been described to modulate Ca(2+)-channels, we investigated the possible participation of 1,4,5-IP3 and/or 1,3,4,5-IP4 in the bradykinin-induced Ca(2+)-influx into cultured porcine aortic endothelial cells. In our experiments bradykinin induced a quick release of Ca2+ from intracellular stores and a longlasting Ca(2+)-influx, which remained constant for at least 15 minutes. In contrast to its effect on [Ca2+]i, bradykinin only transiently elevated 1,4,5-IP3 and 1,3,4,5-IP4 levels. Ten minutes after addition of bradykinin, both 1,4,5-IP3 and 1,3,4,5-IP4 levels returned to basal values, whereas Ca(2+)-influx was still unaltered. Furthermore, preincubation of endothelial cell with phorbol-12-myristate-13-acetate (PMA) abolished the stimulatory effect of bradykinin on the formation of 1,4,5-IP3 and 1,3,4,5-IP4, but did not affect the longlasting Ca(2+)-influx. These data provide evidence that in endothelial cells inositolphosphates are not involved in the regulation of bradykinin-induced longlasting Ca(2+)-influx.