Role Of The Ventromedial Hypothalamic Orexin-A And Orexin-1 Receptors In Regulation Of Gastric Acid Secretion In Conscious Rats

Objective:Orexins cells are mainly located in the hypothalamus,and their fibers are widely distributed in the brain.They are involved in the regulation of feeding,gastric motility,gastric acid secretion and gastric juice secretion.This study aimed to investigate the effects of ventromedial hypothalamic nucleus?VMH?Orexin-A on the secretion of gastric acid and gastric juice in rats and its potential mechanism.Methods:Healthy male Wistar rats were selected,180-220g.The effects of orexin-A on gastric acid and gastric juice secretion were observed by implanting cannulae into the lateral ventricles or VMH and injection of the drugs.And the subcutaneous injection of atropine or intracerebroventricular injection of orexin-A receptor?OX1R?antagonist SB-334867,Y1/Y5 receptor agonist[Pro³⁴]-peptide YY,[cPP^1-7,NPY^19-23,Ala³¹,Aib³²,Gln³⁴]-pancreatic polypeptide,Y1 receptor antagonist GR-231118 and Y5 receptor antagonist CGP-71683,investigated the effects and mechanism of orexin-A on gastric acid and gastric juice secretion in rats.Results:?1?Medium and high doses of orexin-A can significantly promote the secretion of 2h acid and gastric juice in rats,and have significant dose effect dependence?P<0.05⁰.01?,the secretion of gastric acid and gastric juice was strongest in 1h?P<0.05?,suggesting that orexin-A may be involved in the regulation of gastric acid and gastric juice secretion in VMH?satiety center?;?2?The lateral ventricle injection of medium and high doses of SB-334867 can significantly inhibit the secretion of gastric acid and gastric juice in rats,and showed a dose-dependent?P<0.05⁰.01?;IntracerebroventricularinjectionofSB-334867significantly inhibited the effect of orexin-A on the secretion of gastric acid and gastric juice?P<0.05?,suggesting that orexin-A may promote gastric acid secretion and gastric juice secretion through orexin receptor 1;?3?Subcutaneous injection of atropine can significantly inhibit the secretion of gastric acid?P<0.05?,and also completely blocked the effect of ventromedial hypothalamic nucleus injection of orexin-A on gastric acid secretion?P<0.05?,suggesting that the effect of orexin-A on gastric acid secretion may be related to the pathway of cholinergic pathway;?4?Intracerebroventricular microinjection of 8.0?g,16.0?g and 32.0?g GR-231118?Y1 receptor antagonist?in rats decreased gastric acid secretion and gastric juice volume,were dose-dependent?P<0.05⁰.01?,Intracerebroventricular microinjection of 16.0?g and 32.0?g CGP-71683?Y5 receptor antagonist?in rats decreased gastric acid secretion and gastric juice volume,were dose-dependent?P<0.05⁰.01?,16.0?g is the maximum effect concentration of CGP-71683;Pretreatment with GR-231118 or CGP-71683 in the lateral ventricle could partially block the effect of microinjection of orexin-A on the secretion of gastric acid and gastric juice?P<0.05?,suggesting that orexin-A regulates the secretion of gastric acid and gastric juice may be partly through the N PY1 receptor pathway,NPY5 receptor pathway is also involved in the regulation of orexin-A on gastric acid and gastric secretion;?5?Intraventromedial hypothalamic injection of[CPP^1–7,NPY^19–23,Ala³¹,Aib³²,Gln³⁴]–pancreatic polypeptide increased gastric acid secretion,were dose-indepent?P<0.05⁰.01?.Pancreatic polypeptide can increase the effect of orexin-A on gastric acid secretion and gastric juice volume,suggesting that the regulation of orexin-A on gastric acid and gastric juice may depend on the NPY signaling pathway.Conclusion:Orexin-A can be used to promote the secretion of gastric acid and gastric juice in the ventromedial nucleus of the hypothalamus?satiety center?.This effect may be achieved by orexin receptor 1;atropine can not only inhibit gastric acid secretion but also antagonize the effect of orexin-A on gastric acid secretion,the cholinergic nerve pathway is also involved in the regulation of orexin-A on gastric acid secretion.NPY Y1/Y5receptor signaling pathway is also involved in the regulatio n of orexin-A on gastric acid and gastric juice secretion.These results suggest that central neuropeptides or neurotransmitter signaling pathways may interact to participate in the regulation of orexin-A on gastric acid and gastric juice secretion.