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-Trp-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.
Abrão
M S
MS
Departamento de Fisiologia Geral, Universidade de São Paulo, Brazil.
Castrucci
A M
AM
Hadley
M E
ME
Hruby
V J
VJ
D000595:Amino Acid Sequence; D000818:Animals; D002449:Cell Aggregation / Q000187:drug effects / Q000502:physiology; D004075:Diglycerides / Q000037:antagonists & inhibitors / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004524:Eels; D007028:Hypothalamic Hormones; D007295:Inositol Phosphates / Q000037:antagonists & inhibitors; D008543:Melanins / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D008544:Melanocytes / Q000201:enzymology*; D008969:Molecular Sequence Data; D010766:Phosphorylation / Q000187:drug effects; D010907:Pituitary Hormones / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D012867:Skin / Q000201:enzymology; D010738:Type C Phospholipases / Q000378:metabolism*
D004075:Diglycerides; D007028:Hypothalamic Hormones; D007295:Inositol Phosphates; D008543:Melanins; D010907:Pituitary Hormones; C019463:melanin-concentrating hormone; D011493:Protein Kinase C; D010738:Type C Phospholipases