l-Dopa inhibits metoclopramide stimulation of the lower esophageal sphincter in man

Abstract

Opossum lower esophageal sphincter smooth muscle contains inhibitory dopaminergic receptors. Since metoclopramide is a dopaminergic antagonist in many experimental situations, the present study was designed to investigate whether this mechanism could explain the lower esophageal sphincter (LES) stimulating action of metoclopramide in man. The interactions of (1) orall-dopa, a dopamine precursor, and metoclopramide; and (2)l-dopa and the cholinergic agent, bethanechol, on lower esophageal sphincter pressure (LESP) in normal subjects were examined. Orall-dopa significantly inhibited LESP response to either oral metoclopramide 20 mg (P<0.05), or intravenous metoclopramide 20 mg (P<0.05). In contrast,l-dopa did not inhibit the LESP response to subcutaneous bethanechol (0.07 mg/kg). Mean basal LESP measured 50 min after ingestion of 1000 mgl-dopa, 19.3±3.1 mm Hg, was significantly less than basal LESP afterl-dopa placebo, 29.3±4 mm Hg (P<0.01). It is concluded that (1)l-dopa inhibited the metoclopramide-induced rise in LESP but not peak stimulation of LESP by bethanechol; (2) there is evidence for the possibility of LES dopaminergic inhibitory receptors in man; and (3) these data are consistent with the hypothesis that metoclopramide acts on the LES by blocking a dopaminergic pressure-lowering mechanism.