The role of kinin B-1 receptors in the nociception produced by peripheral protein kinase C activation in mice

The peripheral injection of phorbol myristate acetate (PMA) into the mouse paw induces nociception mediated through activation of protein kinase C (PKC). in the present study, we examine the contribution of kinin B I receptor to PMA-induced nociception. Nociception was assessed after intraplantar injection of PMA or the B-1 receptor agonist des-Arg(9)-bradykinin in mice. Mechanisms of nociception were studied using the combination of knockout mice, selective drugs, and measurement of B-1 receptor mRNA and protein levels. Peripheral injection of PMA (50 pmol/paw) induced a nociceptive behaviour that was abolished by selective B I receptor antagonist des-Arg9-Leu8-bradykinin or by the B-1 receptor gene deletion. Moreover, PMA treatment did not alter B-1 receptor rnRNA levels, but greatly increased B-1 receptor protein levels in the mouse paw. the injection of des-Arg9-bradykinin did not cause nociception in naive mice, but produced marked nociception in animals previously treated with a low dose of PMA (0.5 nmol/paw). the co-treatment of PMA with selective PKC or protein synthesis inhibitors, but not with p38 mitogen activated protein kinase (MAPK) or transcription inhibitors significantly reduced des-Arg(9)-bradykinin-induced nociception. On the other hand, the co-administration of selective PKC or p38 MAPK inhibitors, but not of protein synthesis or transcription inhibitors, reduced des-Arg9-bradykinin-induced nociception when evaluated in PMA pre-injected animals. These results suggest that the B 1 receptor exerts a critical role in the nociception caused by PKC activation in peripheral tissues. Since the PKC pathway is downstream of several pro-inflammatory mediators, B, receptor stimulation appears to contribute to the acute inflammatory pain process. (c) 2007 Elsevier B.V. All rights reserved.Univ Fed Santa Catarina, Dept Pharmacol, Florianopolis, SC, BrazilUniv Fed Santa Maria, Dept Chem, BR-97119900 Santa Maria, RS, BrazilUniv Fed Parana, Dept Pharmacol, BR-80060000 Curitiba, Parana, BrazilMax Delbruck Ctr Mol Med, Berlin, GermanyEscola Paulista Med, Dept Biophys, São Paulo, BrazilEscola Paulista Med, Dept Biophys, São Paulo, BrazilWeb of Scienc