title: Brain somatostatin receptor 2 mediates the dipsogenic effect of central somatostatin and cortistatin in rats: role in drinking behavior.
abstract: Intracerebroventricular injection of stable somatostatin (SST) agonists stimulates food and water intake in rats. We investigated the receptor subtype(s) involved in the dipsogenic effect of intracerebroventricular injection of SST agonists, mechanisms of action, and role. In nonfasted and non-water-deprived male rats with chronic intracerebroventricular cannula, intake of water without food or food without water was monitored separately to avoid any interactions compared with intracerebroventricular vehicle. SST-14 and cortistatin (CST-14) (1 μg/rat icv) increased water intake by 3.1- and 2.7-fold, respectively, while both peptides did not alter food intake at 1 h postinjection in the light phase. By contrast, the stable pan-somatostatin agonist ODT8-SST (1 μg/rat icv) increased both water and food intake by 4.9- and 3.7-fold, respectively. S-346-011, a selective receptor 2 (sst2) agonist (1 μg/rat icv) induced water ingestion, while sst1 or sst4 agonist, injected under the same conditions, did not. The sst2 antagonist S-406-028 (1 μg/rat icv) prevented the 1-h water intake induced by intracerebroventricular ODT8-SST and CST-14. Losartan (100 μg/rat icv), an angiotensin receptor 1 (AT1) antagonist, completely blocked the water consumption induced by intracerebroventricular ODT8-SST, whereas intracerebroventricular injection of S-406-028 did not modify the intracerebroventricular ANG II-induced dipsogenic response. The sst2 antagonist reduced by 40% the increase of the 3-h water intake in the early dark phase. These data indicate that SST-14 and CST-14 interact with sst2 to exert a potent dipsogenic effect, which is mediated downstream by angiotensin-AT1 signaling. These data also indicate that sst2 activation by brain SST-14 and/or CST-14 may play an important role in the regulation of drinking behavior.
authors.affiliation: Department of Medicine, CURE/Digestive Diseases Center, Digestive Diseases Division, University of California at Los Angeles, and Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, California; and.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Karasawa
authors.affiliation: Department of Medicine, CURE/Digestive Diseases Center, Digestive Diseases Division, University of California at Los Angeles, and Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, California; and.
authors.forename: Seiichi
authors.initials: S
authors.lastname: Yakabi
authors.affiliation: Department of Medicine, CURE/Digestive Diseases Center, Digestive Diseases Division, University of California at Los Angeles, and Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, California; and.
authors.forename: Lixin
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Medicine, CURE/Digestive Diseases Center, Digestive Diseases Division, University of California at Los Angeles, and Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, California; and.
authors.forename: Andreas
authors.initials: A
authors.lastname: Stengel
authors.affiliation: The Clayton Foundation Laboratories for Peptide Biology, Salk Institute, La Jolla, California.
authors.forename: Jean
authors.initials: J
authors.lastname: Rivier
authors.affiliation: Department of Medicine, CURE/Digestive Diseases Center, Digestive Diseases Division, University of California at Los Angeles, and Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, California; and ytache@mednet.ucla.edu.
authors.forename: Yvette
authors.initials: Y
authors.lastname: Taché
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004326:Drinking / Q000187:drug effects / Q000502:physiology; D004327:Drinking Behavior / Q000187:drug effects*; D004435:Eating / Q000187:drug effects* / Q000502:physiology; D007276:Injections, Intraventricular / Q000379:methods; D008297:Male; D009479:Neuropeptides / Q000008:administration & dosage / Q000494:pharmacology*; D017207:Rats, Sprague-Dawley; D017481:Receptors, Somatostatin / Q000378:metabolism*; D013004:Somatostatin / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D009479:Neuropeptides; D017481:Receptors, Somatostatin; C099323:cortistatin; D013004:Somatostatin; C093733:somatostatin receptor 2
keywords: angiotensin receptor 1; brain; cortistatin; somatostatin agonists; water intake