Motilin, erythromycin, and the gastric migrating motor complex: site of action

Motilin is a putative hormone which induces a premature migrating motor complex when administered exogenously, but the target organ for this hormonal effect is undetermined. Our aim was to determine whether motilin and the motilin agonist, erythromycin, induce a premature migrating motor complex via an effect directly on the stomach. Six dogs underwent splenectomy and ligation of all branches of the splenic artery except the left gastroepiploic and short gastric arteries to the proximal stomach. An intra-arterial catheter was placed in the proximal splenic artery for close intra-arterial injection of motilin and erythromycin directly to the gastric corpus/proximal antrum. After recovery, the minimum effective dose required to induce a premature migrating motor complex was determined for motilin and for erythromycin given close intra-arterially or intravenously (systemically) by monitoring upper gut myoelectric activity. Minimum effective doses of motilin and erythromycin were the same whether given intra-arterially or intravenously. The latency interval or the time to onset of a premature Phase III was less than 2 minutes for intra-arterial or intravenous administration (P > 0.05). The characteristics of induced-Phase HI activity (appearance, duration, velocity) did not differ from spontaneous Phase HI activity (P > 0.05). Although plasma motilin concentrations increased after threshold doses of both motilin and erythromycin, increases in plasma motilin occurred later after erythromycin (lOmin) than after exogenous motilin (3 min). Our findings suggest that motilin initiation of the migrating motor complex does not occur by independent stimulation of putative receptors in the gastric corpus or proximal antrum.