Distinct bradykinin receptors mediate stimulation of prostaglandin synthesis by endothelial cells and fibroblasts.
Bradykinin-stimulated prostaglandin synthesis was investigated in Swiss albino 3T3 fibroblasts (Swiss 3T3 cells) and bovine pulmonary artery endothelial cells (CPAE). Previous studies have indicated that bradykinin stimulates arachidonic acid release in Swiss 3T3 cells by activating phospholipase A2 and by activating phosphatidylcholine-specific phospholipase C in CPAE cells. The dose-response for bradykinin-stimulated prostaglandin synthesis was similar in Swiss 3T3 cells and CPAE cells. Marked differences were found in the effects of several bradykinin analogs in Swiss 3T3 cells and CPAE cells. des-Arg9-bradykinin was a partial agonist in CPAE cells whereas it was completely inactive in Swiss 3T3 cells. [p-chloro-D-Phe6-D-Pro7]-Bradykinin was a full agonist in Swiss 3T3 cells, but only a partial agonist, exhibiting a bell-shaped curve, in CPAE cells. The bradykinin antagonist, [D-Arg0-Hyp3-D-Phe7]-bradykinin, was a several-fold more potent antagonist in Swiss 3T3 cells, compared to CPAE cells. The effects of these bradykinin analogs on prostaglandin synthesis do not fit the previously described BK1, BK2 bradykinin receptor classification. These findings suggest that there are at least two bradykinin receptors which stimulate prostaglandin synthesis. Previous studies have indicated that these two bradykinin receptors may be coupled to different transduction pathways for the release of arachidonate.
D000818:Animals; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology; D002417:Cattle; D004730:Endothelium, Vascular / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism; D011453:Prostaglandins / Q000096:biosynthesis*; D018002:Receptors, Bradykinin; D017981:Receptors, Neurotransmitter / Q000145:classification / Q000187:drug effects / Q000502:physiology*
D011453:Prostaglandins; D018002:Receptors, Bradykinin; D017981:Receptors, Neurotransmitter; C024626:bradykinin, des-Arg(9)-; D001920:Bradykinin