Protein kinase C activation antagonizes melatonin-induced pigment aggregation in Xenopus laevis melanophores.
The pineal hormone, melatonin (5-methoxy N-acetyltryptamine) induces a rapid aggregation of melanin-containing pigment granules in isolated melanophores of Xenopus laevis. Treatment of melanophores with activators of protein kinase C (PKC), including phorbol esters, mezerein and a synthetic diacylglycerol, did not affect pigment granule distribution but did prevent and reverse melatonin-induced pigment aggregation. This effect was blocked by an inhibitor of PKC, Ro 31-8220. The inhibitory effect was not a direct effect on melatonin receptors, per se, as the slow aggregation induced by a high concentration of an inhibitor of cyclic AMP-dependent protein kinase (PKA), adenosine 3',5'-cyclic monophosphothioate, Rp-diastereomer (Rp-cAMPS), was also reversed by PKC activation. Presumably activation of PKC, like PKA activation, stimulates the intracellular machinery involved in the centrifugal translocation of pigment granules along microtubules. alpha-Melanocyte stimulating hormone (alpha-MSH), like PKC activators, overcame melatonin-induced aggregation but this response was not blocked by the PKC inhibitor, Ro 31-8220. This data indicates that centrifugal translocation (dispersion) of pigment granules in Xenopus melanophores can be triggered by activation of either PKA, as occurs after alpha-MSH treatment, or PKC. The very slow aggregation in response to inhibition of PKA with high concentrations of Rp-cAMPS, suggests that the rapid aggregation in response to melatonin may involve multiple intracellular signals in addition to the documented Gi-mediated inhibition of adenylate cyclase.
Sugden
D
D
Biomedical Sciences Division, King's College London, United Kingdom.
Rowe
S J
SJ
D000249:Adenosine Monophosphate / Q000037:antagonists & inhibitors; D000818:Animals; D001692:Biological Transport / Q000502:physiology; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology; D003594:Cytoplasmic Granules / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D007211:Indoles / Q000494:pharmacology; D009074:Melanocyte-Stimulating Hormones / Q000494:pharmacology; D008547:Melanophores / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D008550:Melatonin / Q000494:pharmacology*; D010858:Pigmentation / Q000187:drug effects / Q000502:physiology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013873:Thionucleotides / Q000494:pharmacology; D014982:Xenopus laevis / Q000502:physiology*
D007211:Indoles; D013873:Thionucleotides; C016957:adenosine-3',5'-cyclic phosphorothioate; D000249:Adenosine Monophosphate; D009074:Melanocyte-Stimulating Hormones; D000242:Cyclic AMP; D011493:Protein Kinase C; D008550:Melatonin; D013755:Tetradecanoylphorbol Acetate; C064758:Ro 31-8220