Document Detail


Central administration of pan-somatostatin agonist ODT8-SST prevents abdominal surgery-induced inhibition of circulating ghrelin, food intake and gastric emptying in rats.
MedLine Citation:
PMID:  21569179     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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. Key
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 & INFERENCES: 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:
A Stengel; M Goebel-Stengel; L Wang; A Luckey; E Hu; J Rivier; Y Taché
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Publication Detail:
Type:  Journal Article     Date:  2011-05-13
Journal Detail:
Title:  Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society     Volume:  23     ISSN:  1365-2982     ISO Abbreviation:  Neurogastroenterol. Motil.     Publication Date:  2011 Jul 
Date Detail:
Created Date:  2011-06-17     Completed Date:  2011-12-07     Revised Date:  2013-06-30    
Medline Journal Info:
Nlm Unique ID:  9432572     Medline TA:  Neurogastroenterol Motil     Country:  England    
Other Details:
Languages:  eng     Pagination:  e294-308     Citation Subset:  IM    
Copyright Information:
© 2011 Blackwell Publishing Ltd.
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.
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MeSH Terms
Descriptor/Qualifier:
Abdomen / surgery*
Animals
Brain / drug effects,  physiology
Corticotropin-Releasing Hormone / physiology
Eating / drug effects*,  physiology
Gastric Emptying / drug effects*,  physiology
Ghrelin / blood*
Injections, Intraventricular
Male
Models, Animal
Peptide Fragments / administration & dosage,  pharmacology*
Rats
Rats, Sprague-Dawley
Signal Transduction / physiology
Somatostatin / administration & dosage,  agonists*,  analogs & derivatives*,  pharmacology
Somatostatin-28 / administration & dosage,  pharmacology
Stress, Psychological / physiopathology
Grant Support
ID/Acronym/Agency:
P30 DK041301-13/DK/NIDDK NIH HHS; R01 DK033061-26/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/BIM 23052; 0/Ghrelin; 0/Peptide Fragments; 51110-01-1/Somatostatin; 68374-47-0/somatostatin, octapeptide-Trp(8)-; 75037-27-3/Somatostatin-28; 9015-71-8/Corticotropin-Releasing Hormone
Comments/Corrections

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