title: Central orexin-A increases gastric motility in rats.
abstract: Orexin receptor type-1 (OX1R) is expressed in the dorsal motor nucleus of vagi (DMV). Although orexin-A (OXA) plays an important role in mediating stress responses, it remains unclear how central OXA regulates gastric dysmotility induced by stress. Acute restraint stress (ARS) delays solid gastric emptying via the central corticotropin releasing factor (CRF) and peripheral autonomic neural pathways. We have previously shown that ARS impairs postprandial antro-pyloric coordination and delays solid gastric emptying in rats. We also showed that postprandial gastric contractions were augmented in response to ARS in rats. However, the mechanism of augmented postprandial gastric contractions induced by ARS remains unclear. We tested the hypothesis that augmented gastric motility induced by ARS is mediated via the central OX1R. We also assessed the role of endogenous OXA in the mediation of gastric motility under non-stressed conditions in conscious rats. A strain gauge transducer was implanted on the antrum to record postprandial gastric motility. To investigate whether endogenous OXA is involved in ARS-induced augmented gastric motility, selective OX1R antagonist, SB-334867 (16 μg), was administered intracerebroventricularly (icv). Icv-injection of SB-334867 abolished the augmented gastric contractions induced by ARS. Spontaneous postprandial gastric motility was enhanced by icv-injection of OXA (10 μg), while it was attenuated by icv-injection of SB-3334867. It is suggested that central OXA mediates augmented gastric motility induced by ARS in rats. Central OXA also modulates postprandial gastric contractions in non-stressed conditions.
authors.affiliation: Department of Surgery, Medical College of Wisconsin, WI, USA.
authors.forename: Mehmet
authors.initials: M
authors.lastname: Bülbül
authors.forename: Reji
authors.initials: R
authors.lastname: Babygirija
authors.forename: Kirk
authors.initials: K
authors.lastname: Ludwig
authors.forename: Toku
authors.initials: T
authors.lastname: Takahashi
mesh_terms: D000818:Animals; D001583:Benzoxazoles / Q000008:administration & dosage / Q000494:pharmacology; D005746:Gastric Emptying / Q000187:drug effects*; D005769:Gastrointestinal Motility / Q000187:drug effects*; D007276:Injections, Intraventricular; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology*; D008297:Male; D009287:Naphthyridines; D009479:Neuropeptides / Q000502:physiology*; D000068797:Orexins; D019518:Postprandial Period; D051381:Rats; D017207:Rats, Sprague-Dawley; D012149:Restraint, Physical; D013312:Stress, Physiological / Q000187:drug effects / Q000502:physiology*; D014508:Urea / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: C420062:1-(2-methylbenzoxazol-6-yl)-3-(1,5)naphthyridin-4-yl urea; D001583:Benzoxazoles; D047908:Intracellular Signaling Peptides and Proteins; D009287:Naphthyridines; D009479:Neuropeptides; D000068797:Orexins; D014508:Urea