title: Inhibition of adenylate cyclase activity in the goldfish melanophore is mediated by α₂-adrenoceptors and a pertussis toxin-sensitive GTP-binding protein.
abstract: The signal-transduction system that mediates the melanosome-aggregating response in melanophores of the black-moor goldfish, Carassius auratus, was investigated by examining the inhibition of adenylate cyclase activity mediated by α-adrenoceptors in cultured cells. When the melanophores were incubated with 1 mmol·1⁻¹ 3-isobutyl-1-methylxanthine for 5 min, the intracellular level of cyclic adenosine-3',5'-monophosphate increased two- to three-fold. Norepinephrine at 100 nmol· 1⁻¹ and naphazoline at 1 μmol· 1⁻¹ inhibited the 3-isobutyl-1-methylxanthine-induced accumulation of cyclic adenosine-3',5'-monophosphate in the cells in both the presence and the absence of isoproterenol, a beta-adrenergic agonist. Methoxamine and phenylephrine also reduced the extent of accumulation of cyclic adenosine-3',5'-monophosphate, but only when they were present at relatively high concentrations (above 100 μmol·1⁻¹). The range of concentrations at which norepinephrine inhibited the accumulation of cyclic adenosine-3',5'-monophosphate was consistent with the range at which it induced the aggregation of melanosomes. Pretreatment of the cells with pertussis toxin (1 μg·m1⁻¹) for 15 h or treatment with 100 nmol·1⁻¹ yohimbine (an α₂-adrenergic antagonist) inhibited the effects of the α-adrenergic agonists on both the aggregation of melanosomes and the 3-isobutyl-1-methylxanthine-induced accumulation of cyclic adenosine-3',5'-monophosphate, but prazosin (an α₁-adrenergic antagonist) at 100 nmol·1⁻¹ was not inhibitory. These results indicate that the melanosome-aggregating response of the goldfish melanophore is induced mainly via inhibition of the activity of adenylate cyclase,which occurs as a result of stimulation of a pathway that involves α₂-adrenoceptors and a inhibitory GTP-binding protein.
authors.forename: F
authors.initials: F
authors.lastname: Morishita
authors.forename: A
authors.initials: A
authors.lastname: Shimada
authors.forename: M
authors.initials: M
authors.lastname: Fujimoto
authors.forename: H
authors.initials: H
authors.lastname: Katayama
authors.forename: K
authors.initials: K
authors.lastname: Yamada
mesh_terms: D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000378:metabolism; D000268:Adhesiveness / Q000187:drug effects; D000316:Adrenergic alpha-Agonists / Q000737:chemistry / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000737:chemistry / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000502:physiology; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D029941:Fish Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006054:Goldfish / Q000378:metabolism*; D008547:Melanophores / Q000166:cytology / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D020460:Melanosomes / Q000187:drug effects / Q000378:metabolism; D053141:Organelle Size / Q000187:drug effects; D009994:Osmolar Concentration; D037342:Pertussis Toxin / Q000037:antagonists & inhibitors / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000737:chemistry / Q000494:pharmacology; D018341:Receptors, Adrenergic, alpha-2 / Q000737:chemistry / Q000378:metabolism*; D015290:Second Messenger Systems / Q000187:drug effects*
chemical_list: D000067956:Adenylyl Cyclase Inhibitors; D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D000318:Adrenergic beta-Agonists; D004791:Enzyme Inhibitors; D029941:Fish Proteins; D010726:Phosphodiesterase Inhibitors; D018341:Receptors, Adrenergic, alpha-2; D000242:Cyclic AMP; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases