Leptin directly stimulates catecholamine secretion and synthesis in cultured porcine adrenal medullary chromaffin cells.
Leptin, a protein encoded by the ob gene, is an adipose tissue-derived signaling factor involved in body weight homeostasis. The hypothalamus is a major site of central action for leptin. However, mounting evidence indicates expression of leptin receptor mRNA in various peripheral organs including the adrenal medulla. Therefore, we investigated the effects of leptin on catecholamine secretion and synthesis in cultured porcine adrenal medullary chromaffin cells. We initially confirmed the expression of leptin receptor (Ob-Rb) mRNA in cultured porcine adrenal medullary cells. Murine recombinant leptin (>==50 nM) strongly induced the release of both epinephrine (E) and norepinephrine (NE) from chromaffin cells. Removal of external Ca(2+) significantly suppressed these effects. Also, leptin (>==1 nM) enhanced nicotine-induced increases in E- and NE. Leptin (1, 10, 100 nM) significantly increased tyrosine hydroxylase (TH) (a rate-limiting enzyme in the biosynthesis of catecholamine) mRNA levels in a concentration-dependent manner. Furthermore, leptin (1, 10, 100 nM) significantly induced increases in cAMP levels, suggesting that the stimulatory effects on TH mRNA are mediated, at least in part, by the cAMP/protein kinase A pathway. These results indicate that leptin directly stimulates catecholamine release and synthesis, which in turn may potentiate the anti-obesity effects of leptin.
Takekoshi
K
K
Institute of Clinical Medicine, University of Tsukuba, Ibaraki, Tsukuba, 305-8575, Japan.
Motooka
M
M
Isobe
K
K
Nomura
F
F
Manmoku
T
T
Ishii
K
K
Nakai
T
T
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002352:Carrier Proteins / Q000235:genetics; D002478:Cells, Cultured; D019439:Chromaffin Cells / Q000187:drug effects* / Q000378:metabolism*; D000242:Cyclic AMP / Q000096:biosynthesis; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004837:Epinephrine / Q000096:biosynthesis / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects; D007700:Kinetics; D020738:Leptin; D051379:Mice; D009538:Nicotine / Q000494:pharmacology; D009638:Norepinephrine / Q000096:biosynthesis / Q000378:metabolism*; D011506:Proteins / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D011994:Recombinant Proteins / Q000494:pharmacology; D013552:Swine; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics
D002352:Carrier Proteins; D020738:Leptin; D011506:Proteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D011994:Recombinant Proteins; C515447:leptin receptor, mouse; D009538:Nicotine; D000242:Cyclic AMP; D014446:Tyrosine 3-Monooxygenase; D017868:Cyclic AMP-Dependent Protein Kinases; D002118:Calcium; D009638:Norepinephrine; D004837:Epinephrine