Bradykinin stimulates phospholipid methylation, calcium influx, prostaglandin formation, and cAMP accumulation in human fibroblasts.
The biochemical events that lead to bradykinin stimulation of cAMP accumulation in human fibroblasts were examined. Treatment of human fibroblasts with bradykinin increases phospholipid methylation, Ca2+ influx, arachidonic acid release, prostaglandin formation, and cAMP content. The dose-response curves of bradykinin for the increase in the above changes were similar. In human fibroblasts, exogenous arachidonic acid was mainly incorporated into phosphatidylcholine, followed by phosphatidylserine, phosphatidylethanolamine, and phosphatidylinositol. Bradykinin caused a release of arachidonic acid from methylated phospholipids (phosphatidylcholine) and phosphatidylinositol. 3-Deazaadenosine, a methyltransferase inhibitor, almost completely inhibited bradykinin-stimulated phospholipid methylation and Ca2+ influx and partially reduced arachidonic acid release and prostaglandin formation but had no effect on cAMP formation. Mepacrine, a phospholipase inhibitor, blocked bradykinin-induced arachidonic acid release, prostaglandin release, and cAMP accumulation. Indomethacin, a cyclooxygenase inhibitor, blocked the effect of bradykinin on cAMP accumulation. Prostaglandins E1 and E2, but not F2 alpha, increased accumulation of cAMP. These observations indicate that bradykinin generates cAMP via arachidonic acid release and subsequent formation of prostaglandins. Our findings suggest that arachidonic acid can arise from either phosphatidylcholine synthesized by the methylation pathway or phosphatidylinositol.
D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D001920:Bradykinin / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008745:Methylation; D010743:Phospholipids / Q000378:metabolism*; D011453:Prostaglandins / Q000378:metabolism*; D013997:Time Factors
D001095:Arachidonic Acids; D010743:Phospholipids; D011453:Prostaglandins; D016718:Arachidonic Acid; D000242:Cyclic AMP; D001920:Bradykinin; D002118:Calcium