Nesfatin-1 inhibits gastric acid secretion via a central vagal mechanism in rats.
Nesfatin-1, a novel hypothalamic peptide, inhibits nocturnal feeding behavior and gastrointestinal motility in rodents. The effects of nesfatin-1 on gastrointestinal secretory function, including gastric acid production, have not been evaluated. Nesfatin-1 was injected into the fourth intracerebral ventricle (4V) of chronically cannulated rats to identify a nesfatin dose sufficient to inhibit food intake. Nesfatin-1 (2 μg) inhibited dark-phase food intake, in a dose-dependent fashion, for >3 h. Gastric acid production was evaluated in urethane-anesthetized rats. Nesfatin-1 (2 μg) was introduced via the 4V following endocrine stimulation of gastric acid secretion by pentagastrin (2 μg·kg(-1)·h(-1) iv), vagal stimulation with 2-deoxy-D-glucose (200 mg/kg sc), or no stimulus. Gastric secretions were collected via gastric cannula and neutralized by titration to determine acid content. Nesfatin-1 did not affect basal and pentagastrin-stimulated gastric acid secretion, whereas 2-deoxy-D-glucose-stimulated gastric acid production was inhibited by nesfatin-1 in a dose-dependent manner. c-Fos immunofluorescence in brain sections was used to evaluate in vivo neuronal activation by nesfatin-1 administered via the 4V. Nesfatin-1 caused activation of efferent vagal neurons, as evidenced by a 16-fold increase in the mean number of c-Fos-positive neurons in the dorsal motor nucleus of the vagus (DMNV) in nesfatin-1-treated animals vs. controls (P < 0.01). Finally, nesfatin-induced Ca(2+) signaling was evaluated in primary cultured DMNV neurons from neonatal rats. Nesfatin-1 caused dose-dependent Ca(2+) increments in 95% of cultured DMNV neurons. These studies demonstrate that central administration of nesfatin-1, at doses sufficient to inhibit food intake, results in inhibition of vagally stimulated secretion of gastric acid. Nesfatin-1 activates DMNV efferent vagal neurons in vivo and triggers Ca(2+) signaling in cultured DMNV neurons.
Department of General Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Ze-Feng
ZF
Xia
Danielle M
DM
Fritze
Ji-Yao
JY
Li
Biaoxin
B
Chai
Chao
C
Zhang
Weizhen
W
Zhang
Michael W
MW
Mulholland
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000494:pharmacology*; D004435:Eating / Q000187:drug effects*; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000378:metabolism*; D008297:Male; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D000080866:Nucleobindins; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014630:Vagus Nerve / Q000187:drug effects* / Q000502:physiology
D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; D009419:Nerve Tissue Proteins; C000630652:Nucb1 protein, rat; D000080866:Nucleobindins; D016760:Proto-Oncogene Proteins c-fos; D002118:Calcium