A selective orexin-1 receptor antagonist, SB334867, blocks 2-DG-induced gastric acid secretion in rats.
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.
Yamada
Hiroto
H
Department of General Medicine, Asahikawa Medical College, Asahikawa 078-8510, Japan.
Takahashi
Nobuhiko
N
Tanno
Satoshi
S
Nagamine
Miho
M
Takakusaki
Kaoru
K
Okumura
Toshikatsu
T
D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D003847:Deoxyglucose / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005744:Gastric Acid / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008297:Male; D009479:Neuropeptides / Q000378:metabolism; D064446:Orexin Receptors; D000068797:Orexins; D051381:Rats; D017207:Rats, Sprague-Dawley; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide / Q000037:antagonists & inhibitors*; D013270:Stomach / Q000294:innervation
D000963:Antimetabolites; C000596229:HCRT protein, human; C578627:Hcrtr1 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D064446:Orexin Receptors; D000068797:Orexins; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide; D003847:Deoxyglucose