Nitric oxide inhibits ghrelin-induced cell proliferation and ERK1/2 activation in GH3 cells.
Ghrelin stimulates growth hormone release and cell proliferation, which strongly supports a significant role for this peptide in the control of growth hormone-releasing adenomas function and growth. Nitric oxide can influence the stimulatory effects of ghrelin on growth hormone secretion in growth hormone-releasing adenomas. However, the effect of nitric oxide (NO) on ghrelin-induced cell proliferation and the mechanism of this effect in the adenoma were not clarified. In this study, we observed that ghrelin, at a concentration of 10⁻⁹ to 10⁻⁶ M, significantly increased BrdU incorporation into rat GH3 cells. A NO donor, S-nitroso-N-acetylpenicillamine (SNAP), blunted basal, and ghrelin-induced cell proliferation. A blocker of NO synthase, Nw-nitro-L-arginine methyl ester hydrochloride (NAME), had no influence on these actions. The activation of extracellular signal-regulated kinase (ERK) 1/2 was examined by western blotting. The results showed that SNAP reduced ghrelin-stimulated ERK1/2 activation but NAME had no influence on this activation. Together, this study indicates that NO inhibited ghrelin-induced cell proliferation by blocking ERK1/2 activation in GH3 cells.
Department of Neurosurgery, The First College of Clinical Medical Science, China Three Gorges University, Yichang Center People's Hospital, Yi-Ling-Da-Dao, 183, Yichang 443003, Hubei, People's Republic of China.
Chunlei
C
Tian
Fei
F
Ye
Lei
L
Wang
Yuanguo
Y
Deng
Yuanxun
Y
Dong
Xiaodan
X
Wang
Tongjiang
T
Xu
Ting
T
Lei
Xiongwei
X
Wang
D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D015536:Down-Regulation / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D054439:Ghrelin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009569:Nitric Oxide / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051381:Rats; D052683:Somatotrophs / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology
D054439:Ghrelin; D047428:Protein Kinase Inhibitors; D009569:Nitric Oxide; C535149:Mapk1 protein, rat; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3