title: Central administration of pan-somatostatin agonist ODT8-SST prevents abdominal surgery-induced inhibition of circulating ghrelin, food intake and gastric emptying in rats.
abstract: BACKGROUND
  Activation of brain somatostatin receptors (sst(1-5) ) with the stable pan-sst(1-5) somatostatin agonist, ODT8-SST blocks acute stress and central corticotropin-releasing factor (CRF)-mediated activation of endocrine and adrenal sympathetic responses. Brain CRF signaling is involved in delaying gastric emptying (GE) immediately post surgery. We investigated whether activation of brain sst signaling pathways modulates surgical stress-induced inhibition of gastric emptying and food intake.
  
  
  METHODS
  Fasted rats were injected intracisternally (i.c.) with somatostatin agonists and underwent laparotomy and 1-min cecal palpation. Gastric emptying of a non-nutrient solution and circulating acyl and desacyl ghrelin levels were assessed 50min post surgery. Food intake was monitored for 24 h.
  
  
  RESULTS
  The abdominal surgery-induced inhibition of GE (65%), food intake (73% at 2h) and plasma acyl ghrelin levels (67%) was completely prevented by ODT8-SST (1μg per rat, i.c.). The selective sst(5) agonist, BIM-23052 prevented surgery-induced delayed GE, whereas selective sst(1) , sst(2) , or sst(4) agonists had no effect. However, the selective sst(2) agonist, S-346-011 (1μg per rat, i.c.) counteracted the abdominal surgery-induced inhibition of acyl ghrelin and food intake but not the delayed GE. The ghrelin receptor antagonist, [D-Lys(3) ]-GHRP-6 (0.93mg kg(-1) , intraperitoneal, i.p.) blocked i.p. ghrelin-induced increased GE, while not influencing i.c. ODT8-SST-induced prevention of delayed GE and reduced food intake after surgery.
  
  
  CONCLUSIONS
  ODT8-SST acts in the brain to prevent surgery-induced delayed GE likely via activating sst(5) . ODT8-SST and the sst(2) agonist prevent the abdominal surgery-induced decrease in food intake and plasma acyl ghrelin indicating dissociation between brain somatostatin signaling involved in preventing surgery-induced suppression of GE and feeding response.
authors.affiliation: CURE/Digestive Diseases Research Center, Center for Neurobiology of Stress, Department of Medicine, Digestive Diseases Division at the University of California Los Angeles, and VA Greater Los Angeles Health Care System, Los Angeles, CA 90073, USA.
authors.forename: A
authors.initials: A
authors.lastname: Stengel
authors.forename: M
authors.initials: M
authors.lastname: Goebel-Stengel
authors.forename: L
authors.initials: L
authors.lastname: Wang
authors.forename: A
authors.initials: A
authors.lastname: Luckey
authors.forename: E
authors.initials: E
authors.lastname: Hu
authors.forename: J
authors.initials: J
authors.lastname: Rivier
authors.forename: Y
authors.initials: Y
authors.lastname: Taché
mesh_terms: D000005:Abdomen / Q000601:surgery*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000502:physiology; D003346:Corticotropin-Releasing Hormone / Q000502:physiology; D004435:Eating / Q000187:drug effects* / Q000502:physiology; D005746:Gastric Emptying / Q000187:drug effects* / Q000502:physiology; D054439:Ghrelin / Q000097:blood*; D007276:Injections, Intraventricular; D008297:Male; D023421:Models, Animal; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology; D013004:Somatostatin / Q000008:administration & dosage / Q000819:agonists* / Q000031:analogs & derivatives* / Q000494:pharmacology; D053561:Somatostatin-28 / Q000008:administration & dosage / Q000494:pharmacology; D013315:Stress, Psychological / Q000503:physiopathology
chemical_list: C114314:BIM 23052; D054439:Ghrelin; D010446:Peptide Fragments; D013004:Somatostatin; C017583:somatostatin, octapeptide-Trp(8)-; D053561:Somatostatin-28; D003346:Corticotropin-Releasing Hormone