Two 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'-O-(3-thiotriphosphate) leads to the potentiation of hormone-induced activation of PI turnover, whereas guanosine 5'-O-(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.
Tkachuk
V A
VA
Laboratory of Molecular Endocrinology, National Cardiology Research Center, Moscow, USSR.
Voyno-Yasenetskaya
T A
TA
D000818:Animals; D001920:Bradykinin / Q000378:metabolism / Q000494:pharmacology; D002417:Cattle; D004727:Endothelium / Q000166:cytology / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000502:physiology*; D006150:Guanine Nucleotides / Q000494:pharmacology; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D008168:Lung / Q000166:cytology / Q000378:metabolism*; D010716:Phosphatidylinositols / Q000378:metabolism*; D018002:Receptors, Bradykinin; D011968:Receptors, Histamine / Q000378:metabolism; D017981:Receptors, Neurotransmitter / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D010738:Type C Phospholipases / Q000378:metabolism
D006150:Guanine Nucleotides; D010716:Phosphatidylinositols; D018002:Receptors, Bradykinin; D011968:Receptors, Histamine; D017981:Receptors, Neurotransmitter; D006632:Histamine; D010738:Type C Phospholipases; D019204:GTP-Binding Proteins; D013755:Tetradecanoylphorbol Acetate; D001920:Bradykinin