Influence of motilin on gastric fundus tone and on meal-induced satiety in man: Role of cholinergic pathways

BACKGROUND: Motilin agonists are strong gastroprokinetics, but their impact on symptoms in delayed gastric emptying has been disappointing. It has been speculated that it is due to the contractile effect of motilin agonists on the proximal stomach, but the pathway involved and the symptomatic consequences have been incompletely elucidated. AIMS: To study whether motilin enhances proximal stomach tone and enhances meal-induced satiety and to evaluate whether this effect involves a cholinergic pathway. METHODS: A gastric barostat was used to study, in healthy subjects, the effect of motilin (300 ng/kg/30 min IV) or saline on fasting gastric fundus tone and on post-prandial relaxation. To evaluate the involvement of a cholinergic pathway, atropine (12 mu g/kg/h) was administered intravenously simultaneously with or before and during motilin infusion in the fasting state. Finally, a satiety drinking test was performed in 21 subjects twice after pretreatment with placebo or motilin and with placebo or atropine. RESULTS: Administration of motilin caused a significant increase of fasting fundus tone expressed as decrease of the mean balloon volume (324 +/- 60 mL vs 213 +/- 62 mL, p < 0.05). Simultaneous administration of atropine and motilin did not generate a significant volume change (192 +/- 60 mL vs 181 +/- 83 mL, NS), but pretreatment with atropine alone induced a relaxation, and when motilin was added this revealed an ongoing contraction (192 +/- 24 mL vs 136 +/- 21 mL, p < 0.05). Motilin infusion also inhibited gastric accommodation (p < 0.05 vs placebo) and increased satiety during a satiety drinking test (p < 0.05 vs placebo). CONCLUSIONS: Administration of motilin causes a contraction of the proximal stomach in humans and increases meal-induced satiety. The effect of motilin is atropine-resistant and involves a direct muscular pathway or a non-cholinergic neural pathway.