Document Detail


A selective orexin-1 receptor antagonist, SB334867, blocks 2-DG-induced gastric acid secretion in rats.
MedLine Citation:
PMID:  15698936     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We have previously demonstrated that intracisternal orexin-A potently stimulated gastric acid secretion through the vagus nerve. Considering its stimulatory action on feeding, we hypothesized that orexin-A is a candidate mediator of cephalic phase gastric secretion. It has also been suggested that the stimulation of acid by central orexin-A may be mediated by orexin 1 receptor (OX1R) in the brain. In the present study, we tried to clarify whether endogenously released orexin-A in the brain indeed plays a physiological role in gastric secretion. To address the question, the effects of OX1R antagonist on gastric acid secretion was examined in rats. Intraperitoneal administration of SB334867, a specific OX1R antagonist, by itself did not change gastric acid secretion in pylorus-ligated conscious rats. Pretreatment with SB334867 in a dose of 10 mg/kg completely blocked the stimulated acid output by intracisternal orexin-A but not thyrotropin-releasing hormone, suggesting that SB334867 specifically blocked the action of orexin-A in the brain. 2-Deoxy-D-glucose (2-DG)-induced stimulation of gastric acid output was significantly blocked by pretreatment with intraperitoneal administration of SB334867. These results suggest that endogenously released orexin-A in the brain plays a vital role in central regulation of gastric secretion. Since 2-DG induces central glucoprivation as a hunger state, the present study furthermore supports the speculation that orexin-A may be an important molecule that triggers the cephalic phase gastric acid secretion.
Authors:
Hiroto Yamada; Nobuhiko Takahashi; Satoshi Tanno; Miho Nagamine; Kaoru Takakusaki; Toshikatsu Okumura
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2005-01-24
Journal Detail:
Title:  Neuroscience letters     Volume:  376     ISSN:  0304-3940     ISO Abbreviation:  Neurosci. Lett.     Publication Date:  2005 Mar 
Date Detail:
Created Date:  2005-02-08     Completed Date:  2005-04-01     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7600130     Medline TA:  Neurosci Lett     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  137-42     Citation Subset:  IM    
Affiliation:
Department of General Medicine, Asahikawa Medical College, Asahikawa 078-8510, Japan.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antimetabolites / pharmacology*
Brain / drug effects,  metabolism
Deoxyglucose / pharmacology*
Dose-Response Relationship, Drug
Gastric Acid / metabolism*
Humans
Intracellular Signaling Peptides and Proteins / metabolism
Male
Neuropeptides / metabolism
Rats
Rats, Sprague-Dawley
Receptors, G-Protein-Coupled
Receptors, Neuropeptide / antagonists & inhibitors*
Stomach / innervation
Chemical
Reg. No./Substance:
0/Antimetabolites; 0/Intracellular Signaling Peptides and Proteins; 0/Neuropeptides; 0/Receptors, G-Protein-Coupled; 0/Receptors, Neuropeptide; 0/orexin receptors; 0/orexins; 154-17-6/Deoxyglucose

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