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Stimulatory effect of nobiletin, a citrus polymethoxy flavone, on catecholamine synthesis through Ser(19) and Ser (40) phosphorylation of tyrosine hydroxylase in cultured bovine adrenal medullary cells.
|Title||Stimulatory effect of nobiletin, a citrus polymethoxy flavone, on catecholamine synthesis through Ser(19) and Ser (40) phosphorylation of tyrosine hydroxylase in cultured bovine adrenal medullary cells.|
|Publication Type||Journal Article|
|Year of Publication||2013|
|Authors||Zhang H, Yanagihara N, Toyohira Y, Takahashi K, Inagaki H, Satoh N, Li X, Goa X, Tsutsui M, Takahaishi K|
|Journal||Naunyn-Schmiedeberg's archives of pharmacology|
|Date Published||2013 Sep 17|
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.
|Alternate Journal||Naunyn Schmiedebergs Arch. Pharmacol.|