title: Orexin-1 receptor mediates the increased food and water intake induced by intracerebroventricular injection of the stable somatostatin pan-agonist, ODT8-SST in rats.
abstract: Intracerebroventricular (icv) injection of the stable somatostatin pan-agonist, ODT8-SST induces a somatostatin 2 receptor (sst2) mediated robust feeding response that involves neuropeptide Y and opioid systems in rats. We investigated whether the orexigenic system driven by orexin also plays a role. Food and water intake after icv injection was measured concomitantly in non-fasted and non-water deprived rats during the light phase. In vehicle treated rats (100% DMSO, icv), ODT8-SST (1μg/rat, icv) significantly increased the 2-h food and water intake compared to icv vehicle plus saline (5.1±1.0g vs. 1.2±0.4g and 11.3±1.9mL vs. 2.5±1.2mL, respectively). The orexin-1 receptor antagonist, SB-334867 (16μg/rat, icv) completely inhibited the 2-h food and water intake induced by icv ODT8-SST. In contrast, the icv pretreatment with the selective somatostatin sst2 antagonist, S-406-028, established to block the orexigenic effect of icv ODT8-SST, did not modify the increased food and water intake induced by icv orexin-A (10.7μg/rat). These data indicate that orexin-1 receptor signaling system is part of the brain neurocircuitry contributing to the orexigenic and dipsogenic responses induced by icv ODT8-SST and that orexin-A stimulates food intake independently from brain sst2 activation.
authors.affiliation: Department of Medicine, CURE/Digestive Diseases Center, and Center for Neurobiology of Stress Digestive Diseases Division, University of California at Los Angeles, Los Angeles, CA 90073, USA; Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, CA 90073, USA.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Karasawa
authors.affiliation: Department of Medicine, CURE/Digestive Diseases Center, and Center for Neurobiology of Stress Digestive Diseases Division, University of California at Los Angeles, Los Angeles, CA 90073, USA; Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, CA 90073, USA.
authors.forename: Seiichi
authors.initials: S
authors.lastname: Yakabi
authors.affiliation: Department of Medicine, CURE/Digestive Diseases Center, and Center for Neurobiology of Stress Digestive Diseases Division, University of California at Los Angeles, Los Angeles, CA 90073, USA; Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, CA 90073, USA.
authors.forename: Lixin
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Medicine, CURE/Digestive Diseases Center, and Center for Neurobiology of Stress Digestive Diseases Division, University of California at Los Angeles, Los Angeles, CA 90073, USA; Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, CA 90073, USA. Electronic address: ytache@mednet.ucla.edu.
authors.forename: Yvette
authors.initials: Y
authors.lastname: Taché
mesh_terms: D000818:Animals; D001583:Benzoxazoles / Q000494:pharmacology; D004326:Drinking / Q000187:drug effects*; D004435:Eating / Q000187:drug effects*; D007276:Injections, Intraventricular; D047908:Intracellular Signaling Peptides and Proteins / Q000494:pharmacology; D008297:Male; D009287:Naphthyridines; D009479:Neuropeptides / Q000494:pharmacology; D015282:Octreotide / Q000494:pharmacology; D000068796:Orexin Receptor Antagonists; D064446:Orexin Receptors; D000068797:Orexins; D010446:Peptide Fragments / Q000494:pharmacology*; D017207:Rats, Sprague-Dawley; D017481:Receptors, Somatostatin / Q000819:agonists* / Q000037:antagonists & inhibitors; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000494:pharmacology; D014508:Urea / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: C420062:1-(2-methylbenzoxazol-6-yl)-3-(1,5)naphthyridin-4-yl urea; D001583:Benzoxazoles; C578627:Hcrtr1 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D009287:Naphthyridines; D009479:Neuropeptides; D000068796:Orexin Receptor Antagonists; D064446:Orexin Receptors; D000068797:Orexins; D010446:Peptide Fragments; D017481:Receptors, Somatostatin; C000594154:des-AA(1,4-6,11-13)-(4-nitrophenylalanyl(2)-cysteinyl(3)-tyrosyl(7)-4-aminophenylalanylcarbamoyl(8)-somatostatin-3-(2-naphthyl)-alaninamide; D013004:Somatostatin; C017583:somatostatin, octapeptide-Trp(8)-; D014508:Urea; D015282:Octreotide
keywords: Food intake; ODT8-SST; Orexin-A; SB-334867; Somatostatin 2 receptor; Water intake