Protein kinase C is not necessary for peptide-induced suppression of M current or for desensitization of the peptide receptors.

Frog sympathetic ganglion cells were studied under whole-cell voltage clamp to determine whether protein kinase C (PKC) mediates peptide-induced suppression of M current (IM) or desensitization of peptide receptors. Low concentrations (10 mM) of chicken II luteinizing hormone-releasing hormone (LHRH) or substance P (SP) suppressed IM; in addition, higher concentrations (1 microM) desensitized receptors. Desensitization is homologous (specific to the peptide) and lasts at least 25 min. Two stimulators of PKC, phorbol 12-myristate 13-acetate and dioctanoylglycerol, partially depressed IM and occluded the response to SP but not to LHRH. The two actions of PKC stimulators were blocked by PKC inhibitors (staurosporine, a pseudosubstrate peptide, and H-7), but SP- and LHRH-mediated suppression of IM and receptor desensitization were not affected. Thus, we conclude that PKC is not necessary for normal IM suppression or receptor desensitization.