LHA-DVC Orexin-A Pathway And Regulation Of Gastric Motility And Gastric Motility In Gastric Distraction-sensitive Neurons

Objective: Orexin-A as a novel neuropeptide, which has a wide range of physiological effects and can regulate food intake, energy metabolism, sleep-arousal and gastrointestinal motor function, but the regulatory mechanisms of orexin-A on gastric motility have yet to be elucidated.This study aimed to explore the effects of orexin-A on the gastric-distension(GD) sensitive neurons and gastric motility in the vagus nerve complex(DVC), and the possible regulation by the lateral hypothalamic area(LHA). Retrograde tracing and fluo-immunohistochemistry staining were used to determine projection of nerve fiber and expression of orexin-A.Methods: Retrograde tracing and fluorescent-immunohistochemistry staining were used to observe the neuronal projections between LHA and DVC. Extracellular discharges of single unit neuron were used to observe the effects of orexin-A on the GD neurons. Gastric motility recording in vivo were used to monitor the effects of orexin-A on the amplitude and frequency of gastric constriction in conscious rats. The effect of DVC microinjection of orexin-A on gastric acid secretion will be observed in rats.Results: In retrograde tracing and immunofluorescence study we detected orexin-A/ fluorescent gold(FG) double-labeled neurons in the LHA. We recorded 96 GD sensitive neurons within DVC, of which 58 identified as GD-E neurons and 38 identified as GD-I neurons. After microinjection of orexin-A into DVC, 36 GD-E neurons were excited significantly(P<0.01), while 24 GD-I neurons were significantly inhibited(P <0.01). Pretreatment with orexin-A receptor antagonist SB334867, excitatory effects of orexin-a on GD-E neurons discharge could be blocked(P <0.05), and the inhibitory effect on the GD-I neurons discharge could also be blocked(P <0.05). Electrical stimulation of LHA, 24 out of 36 orexin-A sensitive GD-E neurons in DVC were excited; and 16 out of 24 orexin-A sensitive GD-I neurons were also excited. But pretreatment with SB334867 in DVC, the frequency of GD-E neurons discharge decreased by electrical stimulation of LHA(P <0.05); the frequency of GD-I neurons discharge also declined(P <0.05). Gastric motility study showed that microinjection of orexin-A in DVC, which could increased the amplitude and frequency of gastric contraction in rats, and showed a dose-dependent manner. SB334867 could abolish the effect on gastric motility induced by orexin-A(P <0.05). Electrical stimulation of LHA could promote the gastric motility. Microinjection of orexin-A into DVC, the gastric acid secretion increased in a dose-dependent manner in rats.Conclusion: Orexin-A can regulate GD sensitive neurons discharge and gastric acid secretion and gastric motility in rats, and the effect may be related to orexin signaling pathway.