NEURAL MEDIATION OF THE MOTILIN MOTOR EFFECT ON THE HUMAN ANTRUM

To elucidate the mode of action of motilin on the stimulation of human gastrointestinal motility, we studied the effect of exogenous motilin during muscarinic or serotoninergic pharmacological blockade. Manomet ric recording of the interdigestive antroduodenal motility was carried out in 27 healthy volunteers until the appearance of a spontaneous an tral phase III. The tested blocker was then administered intravenously and was followed 30 min later by a 10-min infusion of synthetic human motilin (50 ng/kg). Motilin administered on a background of saline in duced a premature phase III migrating from the antrum to the duodenum in every tested subject (n = 5). A low dose of atropine (5 mu g . kg(- 1). h(-1) for 90 min) inhibited the motilin effect in two of five subj ects [not significant (NS)], whereas a high dose of atropine (15 mu g/ kg given in 30 min) blocked the motilin-induced premature antral phase III in all instances (n = 5, P < 0.01). Exogenous motilin given with low-dose ondansetron (8 mg given in 15 min followed by 1 mg/h for 90 m in) or high-dose ondansetron (32 mg given in 30 min) was without effec t in three of seven (NS) or in two of five (NS) subjects, respectively . During the administration of 15 mu g/kg atropine, when exogenous mot ilin always failed to induce a premature antral phase III motor, a pha se III-type activity was generated at the duodenum in four of five sub jects. We conclude that the induction by motilin of phase III activity in human antrum is dependent on muscarinic mediation and that the con tractile effect of motilin on human duodenum involves a noncholinergic mechanism, different therefore from the antral pathway.