학술논문

Central administration of pan-somatostatin agonist ODT8-SST prevents abdominal surgery-induced inhibition of circulating ghrelin, food intake and gastric emptying in rats.
Document Type
Article
Source
Neurogastroenterology & Motility. Jul2011, Vol. 23 Issue 7, pe294-e308. 15p. 1 Chart, 8 Graphs.
Subject
*SOMATOSTATIN
*ABDOMINAL surgery
*GHRELIN
*GASTRIC emptying
*INGESTION
*GASTROINTESTINAL hormones
Language
ISSN
1350-1925
Abstract
Activation of brain somatostatin receptors (sst) with the stable pan-sst 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. 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 50 min post surgery. Food intake was monitored for 24 h. The abdominal surgery-induced inhibition of GE (65%), food intake (73% at 2 h) and plasma acyl ghrelin levels (67%) was completely prevented by ODT8-SST (1 μg per rat, i.c.). The selective sst agonist, BIM-23052 prevented surgery-induced delayed GE, whereas selective sst, sst, or sst agonists had no effect. However, the selective sst agonist, S-346-011 (1 μg 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]-GHRP-6 (0.93 mg kg, 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. ODT8-SST acts in the brain to prevent surgery-induced delayed GE likely via activating sst. ODT8-SST and the sst 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. [ABSTRACT FROM AUTHOR]