Differential effects of motilin on interdigestive motility of the human gastric antrum, pylorus, small intestine and gallbladder

Abstract

Motilin was infused in this study with the aim of examining refractory characteristics for motilin stimulation of antral phase III and fasting gallbladder emptying. Moreover, interdigestive pyloric and small intestinal motility from duodenum to ileum were studied, as these may be target organs for motilin. Eight fasting, healthy male volunteers received, on separate subsequent days, repeated infusions of 13leucine-motilin (8 pmol (kg min)(-1) for 5 min) or saline at 30 min after phase IIIs in the duodenum. Interdigestive motility of the antrum, pylorus, duodenum, jejunum and ileum was measured for maximum 10 h by using a 21-lumen perfused catheter. Gallbladder motility was measured by ultrasonography. Motilin infusions induced antral phase IIIs, but only after a preceding phase III of duodenal origin. Under this condition, time-interval to phase III at the duodenal recording site was 30 +/- 13 (SEM) min after motilin, compared with 79 +/- 14 min after saline (P < 0.01), and compared with 121 +/- 13 min for motilin infusion following an antral phase III (P < 0.001). Motilin did not affect small intestinal motility or isolated pyloric pressure waves (IPPWs). However, the number of IPPWs was significantly affected by the origin of the preceding phase III, irrespective of whether motilin or saline was infused. Gallbladder volume decreased significantly within 10 min after each motilin infusion. We conclude that this study clearly demonstrates differential regional effects of motilin. Motilin initiates antral phase IIIs, but stimulation is subject to a refractory period which is clearly prolonged after a preceding antral phase III. Motilin induced gallbladder emptying, however, is not subject to a refractory state. Small intestinal phase IIIs as well as pyloric IPPWs are not affected by motilin.

Manometric evaluation of the motilin receptor agonist camicinal (GSK962040) in humans

“…These observations are in agreement with the well‐known effects of motilin and low doses of the motilin receptor agonist erythromycin on interdigestive motility in man: both were shown to induce a premature phase III with gastric origin . Higher doses of erythromycin no longer induce gastric phase III contractions, but cause prolonged antral contractile activity .…”

“…In the present proof of concept study the motor effect of acutely These observations are in agreement with the well-known effects of motilin and low doses of the motilin receptor agonist erythromycin on interdigestive motility in man: both were shown to induce a premature phase III with gastric origin. 10,13,36,37 Higher doses of erythromycin no longer induce gastric phase III contractions, but cause prolonged antral contractile activity. 13 Pharmacological studies in healthy volunteers provided evidence that induction of phase III is due to stimulation of motilin receptors on neural pathways, whereas the prolonged antral contractile activity induction may reflect activation of muscular motilin receptors.…”

Effect of ginger on gastric motility and symptoms of functional dyspepsia

“…We hypothesized that acceleration of gastric emptying in patients with functional dyspepsia might be accompanied by a reduction in upper gastrointestinal symptoms, and that its action on gastric motility could be mediated via increased secretion of ghrelin [11] or motilin [12] , or by suppression of glucagonlike peptide-1 (GLP-1) [13] .…”

Intragastric acidification inhibits motilin‐induced phase III activity in humans

“…5,6 These effects are dose-dependent and seen at doses from 2 to 4 pmol kg )1 min )1 . 6 A recent study by Luiking et al 7 showed the presence of a refractory period when exogenous infusion of motilin for a short period of time (5 min) was preceded by a phase III of antral origin. In contrast, motilin always induced a phase III when infused over a longer period of time, i.e.…”