Involvement of two different pathways in the motor effects of erythromycin on the gastric antrum in humans

Background - During the interdigestive state in humans, erythromycin 40 mg induces a premature activity front that starts in the stomach, while erythromycin 200 mg induces a prolonged period of enhanced antral contractile activity. Aims - To study the involvement of a cholinergic pathway in the motor effects of erythromycin using the muscarinic antagonist atropine and the neural 5-HT1 receptor agonist sumatriptan. Methods - In 30 healthy volunteers, fasted antroduodenojejunal motor activity was studied by stationary manometry. Placebo (n = 10), atropine (15 mu g/kg intravenous bolus plus 15 mu g/kg/h over 30 minutes; n = 10), or sumatriptan (6 mg subcutaneously; n = 10) was administered, followed by infusion of erythromycin 40 mg or 200 mg. Results - After placebo, erythromycin 40 mg induced a premature activity front with gastric onset after 19.1 (1.7) minutes in all volunteers. After atropine, erythromycin 40 mg failed to induce a premature activity front during a 60 minute period in all volunteers (p < 0.001), while sumatriptan prevented the induction of a premature activity front during a 60 minute period in all but one volunteer (p < 0.005). The number of antral contractions and their mean amplitude in the 60 minutes after erythromycin 200 mg did not differ significantly after atropine or sumatriptan versus placebo. Conclusions - The antral motor effects of erythromycin in humans are mediated via different pathways. The induction of a premature activity front is mediated through activation of an intrinsic cholinergic pathway, while the induction of enhanced antral contractile activity may be mediated via a pathway potentially involving activation of a muscular receptor.