Protein‐Kinase C Mediates MCH Signal Transduction in Teleost, Synbranchus marmoratus, Melanocytes

MCH (melanin concentrating hormone) is a heptadecapeptide, Asp‐Thr‐Met‐Arg‐Cys‐Met‐Val‐Gly‐Arg‐Val‐Tyr‐Arg‐Pro‐Cys‐Tip‐Glu‐Val, which stimulates melanosome (melanin granule) aggregation to a perinuclear position within teleost fish integumental melanocytes, resulting in lightening of the skin. The mechanisms of action of MCH are unknown. Drugs that affect the diacylglycerol/inositol triphosphate pathway were used to investigate the possible roles of this pathway in the mechanisms of action of MCH on Synbranchus marmoratus (teleost) melanocytes. The shift of the dose‐response curve to MCH in the presence of various concentrations of 4‐bromophenacyl bromide and neomycin sulphate, phospholipase C inhibitors, suggests that phospholipase C is stimulated after MCH receptor activation. Low concentrations (10⁻⁹ to 10⁻⁸ M) of the phorbol ester TPA exhibited MCH‐like activity, eliciting a dose‐dependent melanosome aggregation. Higher doses, however, displaced to the right the dose‐response curve to MCH, as did the protein kinase C inhibitors, dibucaine and 1‐(5‐isoquinolinylsulfonyl)‐2‐methylpiperazine (H‐7). These results support the assumption that protein kinase C mediates the pigment aggregating activity of MCH. Both MCH and norepinephrine lightening actions were abolished by beta‐glycerophosphate, a phosphatase inhibitor, suggesting that a protein dephosphorylation occurs during melanosome aggregation, and is, therefore, a common event triggered by MCH and norepinephrine, although both agonists act through separate receptors and exhibit different transduction mechanisms.