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 prostagl...

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Bibliographic Details
Published in:European journal of pharmacology 2003-05, Vol.469 (1-3), p.29-36
Main Authors: JERKINS, David W, SELLERS, Lynda A, FENIUK, Wasyl, HUMPHREY, Patrick P. A
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Bradykinin - pharmacology
Cells, Cultured
Dinoprostone - metabolism
Female
Male
Medical sciences
Neurons - drug effects
Neurons - metabolism
Rats
Rats, Wistar
Receptor, Bradykinin B2 - agonists
Receptor, Bradykinin B2 - metabolism
Trigeminal Ganglion - drug effects
Trigeminal Ganglion - metabolism
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Summary: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.
ISSN:0014-2999
1879-0712
DOI:10.1016/s0014-2999(03)01732-1