Regulation by bradykinin of phosphoinositide metabolism in the endothelial cells of the pulmonary artery.
The effect of the vasodilatory peptide bradykinin on the regulation of phosphoinositide metabolism in endothelial cells was investigated. Activation of phosphoinositide metabolism by bradykinin in the endothelium of the bovine pulmonary artery was not blocked by pertussis toxin, which ADP-ribosylates a membrane protein of molecular mass 40 kDa, but botulinum toxin, which ADP-ribosylates a membrane protein of molecular mass 24 kDa, fully blocked bradykinin-stimulated phosphoinositide metabolism. The effect of bradykinin was potentiated by guanosine 5'-O-(3-thiotriphosphate) (GTP-gamma-S), an activator of GTP-binding proteins, and inhibited by guanosine 5'-O-(2-thiodiphosphate) (GDP-beta-S), an inhibitor of GTP-binding proteins. Activation of phosphoinositide metabolism by bradykinin was fully blocked by a B2-receptor antagonist, whereas a B1-receptor antagonist did not affect bradykinin action. It is concluded that the B2-receptor in endothelial cells is coupled to phospholipase C via a GTP-binding protein, which is a substrate for botulinum toxin.
Voino-Yasenetskaya
T A
TA
Institute of Experimental Cardiology, Academy of Medical Sciences of the USSR, Moscow.
Bochkov
V N
VN
Tkachuk
V A
VA
Ryan
U S
US
D000818:Animals; D001905:Botulinum Toxins / Q000494:pharmacology; D001920:Bradykinin / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002417:Cattle; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D004730:Endothelium, Vascular / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000378:metabolism; D007295:Inositol Phosphates / Q000378:metabolism*; D007700:Kinetics; D037342:Pertussis Toxin; D011651:Pulmonary Artery; D018002:Receptors, Bradykinin; D017981:Receptors, Neurotransmitter / Q000378:metabolism; D015290:Second Messenger Systems; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D007295:Inositol Phosphates; D018002:Receptors, Bradykinin; D017981:Receptors, Neurotransmitter; D010566:Virulence Factors, Bordetella; D037342:Pertussis Toxin; D001905:Botulinum Toxins; D019204:GTP-Binding Proteins; D001920:Bradykinin; D002118:Calcium