title: Abdominal surgery inhibits circulating acyl ghrelin and ghrelin-O-acyltransferase levels in rats: role of the somatostatin receptor subtype 2.
abstract: Clinical studies are evaluating the efficacy of synthetic ghrelin agonists in postoperative ileus management. However, the control of ghrelin secretion under conditions of postoperative gastric ileus is largely unknown. Peripheral somatostatin inhibits ghrelin secretion in animals and humans. We investigated the time course of ghrelin changes postsurgery in fasted rats and whether somatostatin receptor subtype 2 (sst(2)) signaling is involved. Abdominal surgery (laparotomy and 1-min cecal palpation) induced a rapid and long-lasting decrease in plasma acyl ghrelin levels as shown by the 64, 67, and 59% reduction at 0.5, 2, and 5 h postsurgery, respectively, compared with sham (anesthesia alone for 10 min, P < 0.05). Levels were partly recovered at 7 h and fully restored at 24 h. The percentage of acyl ghrelin reduction was significantly higher than that of desacyl ghrelin at 2 h postsurgery and not at any other time point. This was associated with a 48 and 23% decrease in gastric and plasma ghrelin-O-acyltransferase protein concentrations, respectively (P < 0.001). Ghrelin-positive cells in the oxyntic mucosa expressed sst(2a) receptor and the sst(2) agonist S-346-011 inhibited fasting acyl ghrelin levels by 64 and 77% at 0.5 and 2 h, respectively. The sst(2) antagonist S-406-028 prevented the abdominal surgery-induced decreased circulating acyl ghrelin but not the delayed gastric emptying assessed 0.5 h postinjection. These data show that activation of sst(2) receptor located on gastric X/A-like cells plays a key role in the rapid inhibition of circulating acyl ghrelin induced by abdominal surgery while not being primarily involved in the early phase of postoperative gastric ileus.
authors.affiliation: Department of Medicine, CURE Digestive Diseases Research Center, Digestive Diseases Division at University of California Los Angeles, USA.
authors.forename: Andreas
authors.initials: A
authors.lastname: Stengel
authors.forename: Miriam
authors.initials: M
authors.lastname: Goebel-Stengel
authors.forename: Lixin
authors.initials: L
authors.lastname: Wang
authors.forename: Almaas
authors.initials: A
authors.lastname: Shaikh
authors.forename: Nils W G
authors.initials: NW
authors.lastname: Lambrecht
authors.forename: Jean
authors.initials: J
authors.lastname: Rivier
authors.forename: Yvette
authors.initials: Y
authors.lastname: Taché
mesh_terms: D000005:Abdomen / Q000601:surgery*; D000217:Acyltransferases / Q000097:blood* / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D005746:Gastric Emptying / Q000502:physiology*; D005753:Gastric Mucosa / Q000378:metabolism; D054439:Ghrelin / Q000097:blood*; D045823:Ileus / Q000503:physiopathology*; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017481:Receptors, Somatostatin / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D013272:Stomach Diseases / Q000503:physiopathology*; D013997:Time Factors
chemical_list: D054439:Ghrelin; D012333:RNA, Messenger; D017481:Receptors, Somatostatin; C422650:ghrelin, des-n-octanoyl; C093733:somatostatin receptor 2; D000217:Acyltransferases; C534462:ghrelin O-acyltransferase, rat