The role of kinin B-1 receptors in the nociception produced by peripheral protein kinase C activation in mice
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2008-03-01
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Ferreira, Juliano
Triches, Karen M.
Medeiros, Rodrigo
Cabrini, Daniela A.
Mori, Marcelo A. S. [UNIFESP]
Pesquero, Joao B. [UNIFESP]
Bader, Michael
Calixto, Joao B.
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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.
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Neuropharmacology. Oxford: Pergamon-Elsevier B.V., v. 54, n. 3, p. 597-604, 2008.