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.