title: Mechanisms of action of melanin-concentrating hormone in the teleost fish erythrophoroma cell line (GEM-81).
abstract: Melanin-concentrating hormone (MCH) evokes an increase of GEM-81 cell proliferation. This action of 10(-6)M MCH was inhibited in the presence of the following blockers: U-73122 (phospholipase C), Ro-31-8220 (PKC) or KN-93 (Ca(2+)/calmodulin-dependent kinase). The more selective PKC inhibitors, HBDDE and Go-6983, which block, respectively, PKC alpha/gamma isoform and beta1 isoform, were used. HBDDE was ineffective whereas Go-6983 reversed the proliferative response promoted by MCH. Flow cytometry assays demonstrated that MCH induces a slow and long-lasting rise in intracellular calcium, which can be blocked by U-73122. Our results also show a cAMP increase evoked by MCH. Our data support the assumption that MCH exerts its effect on GEM-81 erythrophoroma cells through activation of phosholipase C, beta1 PKC, and Ca(2+)/calmodulin-dependent PKC, and eliciting a slow, long-lasting rise in calcium, which may trigger the proliferative signal.
authors.affiliation: Departamento de Fisiologia, Instituto de Biociências, Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Mauro César
authors.initials: MC
authors.lastname: Isoldi
authors.forename: Mara Helena
authors.initials: MH
authors.lastname: de Pina Benabou
authors.forename: Robert Ivan
authors.initials: RI
authors.lastname: Schumacher
authors.forename: Carolina Costa
authors.initials: CC
authors.lastname: Góis
authors.forename: Ana Cristina
authors.initials: AC
authors.lastname: Scarparo
authors.forename: Nancy Amaral
authors.initials: NA
authors.lastname: Rebouças
authors.forename: Maria Aparecida
authors.initials: MA
authors.lastname: Visconti
mesh_terms: D000818:Animals; D001596:Benzylamines / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004963:Estrenes / Q000494:pharmacology; D005393:Fish Diseases / Q000473:pathology; D006054:Goldfish; D007028:Hypothalamic Hormones / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology; D008543:Melanins / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D010907:Pituitary Hormones / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011760:Pyrrolidinones / Q000494:pharmacology; D012878:Skin Neoplasms / Q000473:pathology / Q000662:veterinary; D013449:Sulfonamides / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors; D000096926:Benzenesulfonamides
chemical_list: D001596:Benzylamines; D017868:Cyclic AMP-Dependent Protein Kinases; D004791:Enzyme Inhibitors; D004963:Estrenes; D007028:Hypothalamic Hormones; D007211:Indoles; D008543:Melanins; D010907:Pituitary Hormones; D011493:Protein Kinase C; D011760:Pyrrolidinones; D013449:Sulfonamides; D010738:Type C Phospholipases; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; C072105:KN 93; D000096926:Benzenesulfonamides; C019463:melanin-concentrating hormone; C064758:Ro 31-8220