2 TYPES OF G-PROTEINS INVOLVED IN REGULATION OF PHOSPHOINOSITIDE TURNOVER IN PULMONARY ENDOTHELIAL-CELLS

The involvement of G proteins in hormonal regulation of phospholipase C in bovine pulmonary arterial endothelial cells and human umbilical vein endothelial cells has been investigated. Histamine and bradykinin stimulated phosphoinositol (PI) turnover in a dose-dependent manner, and phorbol-myristate-acetate inhibited hormone-dependent activation of PI turnover, indicating a feedback control of this process. Activation of PI turnover by histamine and bradykinin is guanine nucleotide-dependent. Stimulation of the endothelial cell G proteins by guanosine 5'-0-(3-thiotriphosphate) leads to the potentiation of hormone-induced activation of PI turnover, whereas guanosine 5'-0-(2-thiodiphosphate), which inactivates G proteins, blocks the hormone-dependent PI turnover. Pertussis toxin blocked the histamine-dependent stimulation but did not affect the bradykinin-dependent stimulation of phospholipase C. By contrast, botulinum toxin (C2 + C3 components) blocked the bradykinin-dependent stimulation of phospholipase C but did not affect the histamine-dependent stimulation of this enzyme. These data suggest that at least two different G proteins are involved in hormone-dependent stimulation of phospholipase C in endothelial cells.