title: Stimulation of catecholamine synthesis in cultured bovine adrenal medullary cells by leptin.
abstract: Recently, we characterized leptin receptors in bovine adrenal medullary cells (Yanagihara et al. 2000). Here we report the stimulatory effect of leptin on catecholamine synthesis in the cells. Incubating cells with leptin (10 nM) for 20 min increased the synthesis of 14C-catecholamines from [14C]tyrosine, but not from L-3,4-dihydroxyphenyl [3-14C]alanine. The stimulation of catecholamine synthesis in the cells by leptin was associated with the phosphorylation and activation of tyrosine hydroxylase, the rate-limiting enzyme of catecholamine biosynthesis. The incubation of cells with leptin resulted in a rapid activation of the mitogen-activated protein kinases (MAPKs). An inhibitor of MAPK kinase, U0126, nullified the stimulatory effect of leptin on the synthesis of 14C-catecholamines. Leptin potentiated the stimulatory effect of acetylcholine on 14C-catecholamine synthesis, whereas leptin failed to enhance the phosphorylation and activation of tyrosine hydroxylase induced by acetylcholine. These findings suggest that leptin stimulates catecholamine synthesis via the activation of tyrosine hydroxylase by two different mechanisms, i.e., one is dependent on tyrosine hydroxylase phosphorylation mediated through the MAPK pathway and the second is independent of enzyme phosphorylation.
authors.affiliation: Department of Pharmacology, University of Occupational and Environmental Health, School of Medicine, Kitakyushu, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Utsunomiya
authors.forename: N
authors.initials: N
authors.lastname: Yanagihara
authors.forename: E
authors.initials: E
authors.lastname: Tachikawa
authors.forename: T B
authors.initials: TB
authors.lastname: Cheah
authors.forename: K
authors.initials: K
authors.lastname: Kajiwara
authors.forename: Y
authors.initials: Y
authors.lastname: Toyohira
authors.forename: S
authors.initials: S
authors.lastname: Ueno
authors.forename: F
authors.initials: F
authors.lastname: Izumi
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000313:Adrenal Medulla / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D002070:Butadienes / Q000494:pharmacology; D002395:Catecholamines / Q000096:biosynthesis*; D002417:Cattle; D002478:Cells, Cultured; D004295:Dihydroxyphenylalanine / Q000378:metabolism; D004789:Enzyme Activation / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015759:Ionomycin / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology; D020738:Leptin / Q000494:pharmacology*; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009570:Nitriles / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D011494:Protein Kinases / Q000378:metabolism; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D002070:Butadienes; D002395:Catecholamines; D004791:Enzyme Inhibitors; D007476:Ionophores; D020738:Leptin; D009570:Nitriles; C113580:U 0126; D015759:Ionomycin; D004295:Dihydroxyphenylalanine; D014446:Tyrosine 3-Monooxygenase; D011494:Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D020929:Mitogen-Activated Protein Kinase Kinases; D000109:Acetylcholine