EVIDENCE THAT PROTEIN-KINASE-C ACTIVATION IS INVOLVED IN THE EXCITATORY AND FACILITATORY EFFECTS OF BRADYKININ ON CANINE VISCERAL NOCICEPTORS IN-VITRO

The involvement of protein kinase (PK) C activation in the effects of bradykinin (BK) on peripheral nociceptors, polymodal receptors, was ex amined using canine testis-spermatic nerve preparations in vitro. Phor bol 12,13-dibutyrate 0.1 mu M, which activates PKC, suppressed the BK- induced excitation when applied for 3-5 min prior to BK application, b ut facilitated it when applied simultaneously with BK. Neither effect was induced by an inactive phorbol ester, 4 alpha-phorbol 12, 13-didec anoate, demonstrating that both effects were mediated through the acti vation of PKC. In addition, staurosporine 1 mu M, a PK inhibitor, supp ressed both BK-induced excitation and facilitation of the heat respons e of testicular polymodal receptors without influencing on-going activ ities and the heat response itself. These results suggest that PKC act ivation is involved in the excitatory and facilitatory effects of BK o n peripheral nociceptors. (C) 1997 Elsevier Science Ireland Ltd.