title: Stimulatory effect of nobiletin, a citrus polymethoxy flavone, on catecholamine synthesis through Ser19 and Ser40 phosphorylation of tyrosine hydroxylase in cultured bovine adrenal medullary cells.
abstract: We previously reported the dual effects of nobiletin, a compound of polymethoxy flavones found in citrus fruits, on catecholamine secretion in cultured bovine adrenal medullary cells. Here, we report the effects of nobiletin on catecholamine synthesis in the cells. Nobiletin increased the synthesis of (14)C-catecholamines from [(14)C]tyrosine in a time (20-30 min)- and concentration (1.0-100 μM)-dependent manner. Nobiletin (10-100 μM) also activated tyrosine hydroxylase activity. The stimulatory effect of nobiletin on (14)C-catecholamine synthesis was not observed when extracellular Ca(2+) was not present in the incubation medium. Protein kinase inhibitors including H-89, an inhibitor of cyclic AMP-dependent protein kinase, and KN-93, an inhibitor of Ca(2+)/calmodulin-dependent protein kinase II, suppressed the stimulatory effects of nobiletin on catecholamine synthesis as well as tyrosine hydroxylase activity. Nobiletin also induced the phosphorylation of tyrosine hydroxylase at Ser(19) and Ser(40). Nobiletin (1.0-100 μM) inhibited (14)C-catecholamine synthesis induced by acetylcholine. The present findings suggest that nobiletin, by itself, stimulates catecholamine synthesis through tyrosine hydroxylase phosphorylation at Ser(19) and Ser(40), whereas it inhibits catecholamine synthesis induced by acetylcholine in bovine adrenal medulla.
authors.affiliation: Research Center of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.
authors.forename: Han
authors.initials: H
authors.lastname: Zhang
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Yanagihara
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Toyohira
authors.forename: Keita
authors.initials: K
authors.lastname: Takahashi
authors.forename: Hirohide
authors.initials: H
authors.lastname: Inagaki
authors.forename: Noriaki
authors.initials: N
authors.lastname: Satoh
authors.forename: Xiaoja
authors.initials: X
authors.lastname: Li
authors.forename: Xiumei
authors.initials: X
authors.lastname: Goa
authors.forename: Masato
authors.initials: M
authors.lastname: Tsutsui
authors.forename: Kojiro
authors.initials: K
authors.lastname: Takahaishi
mesh_terms: D000313:Adrenal Medulla / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D002395:Catecholamines / Q000096:biosynthesis*; D002417:Cattle; D002478:Cells, Cultured; D002957:Citrus; D004305:Dose-Response Relationship, Drug; D047309:Flavones / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects / Q000502:physiology; D012694:Serine / Q000378:metabolism*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism*
chemical_list: D002395:Catecholamines; D047309:Flavones; D012694:Serine; C008661:nobiletin; D014446:Tyrosine 3-Monooxygenase; C043562:flavone
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