Motilin induces gall bladder emptying and antral contractions in the fasted state in humans

Background-Animal studies have shown that motilin affects pall bladder motility. In humans, no effect has been shown, but erythromycin, a motilin receptor agonist, induces gall bladder emptying. Aims-To explore the effect of increasing doses of exogenous motilin on gall bladder volume and antral contractility in the fasted state in humans. Methods-After an overnight fast, eight healthy men received increasing intravenous doses of Leu(13)-motilin (KW-5139) or 0.9% NaCl in a double blind, randomised fashion. Gall bladder volume and antral contraction frequency were determined by ultrasonography. Results-Infusion of motilin increased plasma motilin levels. Motilin induced a reduction in gall bladder volume of 8.0 (5.0)%, 17.1 (5.0)%, 18.5 (4.7)%, and 16.1 (4.9)% of baseline volume at the end of infusion of 2, 4, ,8 and 16 pmol/kg/min respectively, compared with mean stable gall bladder volumes during placebo infusion (p<0.05). Antral contraction frequency increased during motilin infusion, but not during placebo infusion (p<0.05). Conclusions-Exogenous motilin reducted fasting gall bladder volume and increased antral contractions. After reaching maximal reduction, the gall bladder volume did not decrease further duping continuous motilin infusion at higher doses and stayed at the same reduced volume. The degree of gall bladder volume reduction during motilin infusion mimicked gall bladder emptying preceding antral phase Ill activity of the migrating motor complex in humans. This study indicates that motilin may play a physiological role in the regulation of gall bladder emptying in the fasted state.