Coupling of bradykinin receptors to phospholipase C in cultured fibroblasts is mediated by a G-protein.
In cultured foreskin fibroblasts, bradykinin stimulates inositol phosphate generation, arachidonic acid release, and Na+/H+ exchange, with doses of 1-3 nM yielding half-maximal stimulation. Binding of 3H-bradykinin to these cells demonstrates a single receptor site with a Kd of 2.0 nM and a Bmax of 91 fmoles/mg protein. Bradykinin analogs of the B2 type inhibit this binding. GTP synergizes with bradykinin to stimulate phosphatidylinositol turnover in permeabilized fibroblasts and GTP-gamma-S decreases the Bmax of bradykinin binding to fibroblast membranes, indicating that a G-protein couples the receptor to phospholipase C. Pretreatment of fibroblasts with either cholera or pertussis toxin enhances bradykinin stimulation of inositol phosphate accumulation.
Etscheid
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BG
Department of Pharmacological and Physiological Sciences, University of Chicago, Illinois 60637.
Villereal
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ML
D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D001920:Bradykinin / Q000378:metabolism; D002478:Cells, Cultured; D002772:Cholera Toxin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000378:metabolism* / Q000502:physiology / Q000648:ultrastructure; D019204:GTP-Binding Proteins / Q000494:pharmacology*; D006801:Humans; D007295:Inositol Phosphates / Q000378:metabolism; D008297:Male; D037342:Pertussis Toxin; D018002:Receptors, Bradykinin; D017981:Receptors, Neurotransmitter / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism; D010738:Type C Phospholipases / Q000378:metabolism*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D001095:Arachidonic Acids; D007295:Inositol Phosphates; D018002:Receptors, Bradykinin; D017981:Receptors, Neurotransmitter; D010566:Virulence Factors, Bordetella; D016718:Arachidonic Acid; D002772:Cholera Toxin; D012964:Sodium; D037342:Pertussis Toxin; D010738:Type C Phospholipases; D019204:GTP-Binding Proteins; D001920:Bradykinin