title: Norepinephrine induces apoptosis in skin melanophores by attenuating cAMP-PKA signals via alpha2-adrenoceptors in the medaka, Oryzias latipes.
abstract: The density of skin melanophores in many teleost fish decreases during long-term adaptation to a white background. Using the medaka, Oryzias latipes, we previously reported that apoptosis is responsible for the decrease in melanophores, and that a sympathetic neurotransmitter, norepinephrine (NE), induces their apoptosis in skin tissue cultures. In this study, we show that NE-induced apoptosis of melanophores is mediated by the activation of alpha2-adrenoceptors. Clonidine, an alpha2-adrenoceptor agonist, induced apoptotic melanophore death in skin organ culture, while phenylephrine, an alpha1-adrenoceptor agonist, had no effect. NE-induced apoptosis was diminished by an alpha2-adrenoceptor antagonist, yohimbine, but an alpha1-adrenoceptor antagonist, prazosin, did not abrogate the effect of NE. Furthermore, forskolin inhibited NE-induced apoptosis, while an inhibitor of PKA, H-89, mimicked the effect of NE. These results suggest that NE induces apoptosis in melanophores by attenuating cAMP-PKA signaling via alpha2-adrenoceptors.
authors.affiliation: Department of Biomolecular Science, Faculty of Science, Toho University, Funabashi, Chiba, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Uchida-Oka
authors.forename: M
authors.initials: M
authors.lastname: Sugimoto
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D003000:Clonidine / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D046508:Culture Techniques; D000242:Cyclic AMP / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D008547:Melanophores / Q000187:drug effects* / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology*; D009842:Oligopeptides / Q000494:pharmacology; D009990:Oryzias / Q000502:physiology*; D010656:Phenylephrine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D020033:Protein Isoforms; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D012867:Skin / Q000166:cytology / Q000378:metabolism; D012880:Skin Pigmentation / Q000502:physiology; D013449:Sulfonamides; D015016:Yohimbine / Q000494:pharmacology
chemical_list: D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D015853:Cysteine Proteinase Inhibitors; D007546:Isoquinolines; D009842:Oligopeptides; D020033:Protein Isoforms; D018341:Receptors, Adrenergic, alpha-2; D013449:Sulfonamides; C108637:aspartyl-glutamyl-valyl-aspartal; D005576:Colforsin; D010656:Phenylephrine; D015016:Yohimbine; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide; D003000:Clonidine; D009638:Norepinephrine; D011224:Prazosin