Characterization of bradykinin-induced prostaglandin E2 release from cultured rat trigeminal ganglion neurones.
Bradykinin and prostaglandins are both local mediators strongly implicated in pain and inflammation. Here, we have investigated the effects of bradykinin on the release of prostaglandin E(2) from cultured neurones derived from adult rat trigeminal ganglia. Bradykinin was a potent inducer of prostaglandin E(2) release, an effect that was likely mediated by bradykinin B(2) receptors, as the bradykinin-induced prostaglandin E(2) release was attenuated by the bradykinin B(2) receptor-selective antagonist, arginyl-L-prolyl-trans-4-hydroxy-L-prolylglycyl-3-(2-thienyl)-L-alanyl-L-seryl-D-1,2,3,4-tetrahydro-3-isoquinolinecarbonyl-L-(2 alpha, 3 beta, 7a beta)-octahydro-1H-indole-2-carbonyl-L-arginine (HOE 140), but not by the bradykinin B(1) receptor-selective antagonist, des-Arg(9),[Leu(8)]-bradykinin. Furthermore, bradykinin-induced prostaglandin E(2) release was inhibited following treatment with the phospholipase A(2) inhibitor, arachidonyltrifluoromethyl ketone (AACOCF(3)), the nonselective cyclooxygenase inhibitor, piroxicam, the mitogen-activated protein kinase kinase-1 (MEK1) inhibitor, 2'-amino-3'-methoxyflavone (PD98059), and the protein kinase C inhibitor, bisindolylmaleimide XI (Ro320432). Taken together, these data suggest that bradykinin, acting via bradykinin B(2) receptors, induces prostaglandin E(2) release from trigeminal neurones through the protein kinase C and mitogen-activated protein kinase-dependent activation of phospholipase A(2) and consequent stimulation of cyclooxygenases.
Jenkins
David W
DW
Glaxo Institute of Applied Pharmacology, Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge CB2 1PD, UK. david.jenkins@astrazeneca.com
Sellers
Lynda A
LA
Feniuk
Wasyl
W
Humphrey
Patrick P A
PP
D000818:Animals; D001920:Bradykinin / Q000494:pharmacology*; D002478:Cells, Cultured; D015232:Dinoprostone / Q000378:metabolism*; D005260:Female; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D043782:Receptor, Bradykinin B2 / Q000819:agonists / Q000378:metabolism; D012668:Trigeminal Ganglion / Q000187:drug effects* / Q000378:metabolism
D043782:Receptor, Bradykinin B2; D015232:Dinoprostone; D001920:Bradykinin