Possible contribution of protein kinase C in the effects of histamine on the visceral nociceptor activities in vitro.
To clarify the possible contribution of protein kinase C activation in histamine-induced excitation and sensitization of the heat response of testicular polymodal receptors, the effects of staurosporine, a protein kinase C inhibitor, and phorbol 12,13-dibutyrate, a protein kinase C activating phorbol ester, were studied in visceral polymodal receptors. Single polymodal receptor activities were recorded in vitro from testis-spermatic nerve preparations obtained from deeply anesthetized dogs (pentobarbital sodium, 30 mg/kg, i.v.). Histamine (10 microM)-induced excitation and facilitation of the heat response of polymodal receptors were both suppressed by staurosporine (1 microM), suggesting that activation of protein kinase C is involved in both these effects of histamine. Application of phorbol 12,13-dibutyrate (0.1 microM) mixed with histamine increased the histamine-induced excitation, whereas a 5 min application of phorbol 12,13-dibutyrate before histamine suppressed it. These results suggest that phorbol 12,13-dibutyrate-activated protein kinase C has inactivation as well as activation effects on the intracellular cascade connected to histamine receptors, and that the former has a slower time course.
Department of Neural Regulation, Research Institute of Environmental Medicine, Nagoya University, Japan. mizu@riem.nagoya-u.ac.jp
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D000818:Animals; D004285:Dogs; D004789:Enzyme Activation / Q000502:physiology; D006632:Histamine / Q000494:pharmacology*; D006633:Histamine Antagonists / Q000494:pharmacology; D006358:Hot Temperature; D066298:In Vitro Techniques; D008297:Male; D009619:Nociceptors / Q000187:drug effects* / Q000502:physiology*; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D011493:Protein Kinase C / Q000502:physiology*; D013085:Spermatic Cord / Q000294:innervation; D019311:Staurosporine / Q000494:pharmacology; D013737:Testis / Q000294:innervation; D013997:Time Factors; D014781:Viscera / Q000294:innervation*
D006633:Histamine Antagonists; D015240:Phorbol 12,13-Dibutyrate; D006632:Histamine; D011493:Protein Kinase C; D019311:Staurosporine