Regionally dependent neuromuscular functions of motilin and 5-HT₄ receptors in human isolated esophageal body and gastric fundus.

Abstract

Motilin agonists promote human gastric motility and cholinergic activity, but excitatory and inhibitory actions are reported in the esophagus. The effect of 5-HT₄ agonists in esophagus is also unclear. Perhaps the use of drugs with additional actions explains the variation. The aim, therefore, was to examine how motilin and prucalopride, selective motilin and 5-HT₄ receptor agonists, modulate neuromuscular functions in human esophagus and gastric fundus. Electrical field stimulation (EFS) evoked nerve-mediated contractions of circular and longitudinal muscle from human esophageal body and circular muscle from gastric fundus. In esophageal circular muscle EFS evoked brief contraction, followed by another contraction on termination of EFS, each prevented by atropine. Nitric oxide synthase inhibition facilitated contraction during EFS and the overall contraction became monophasic. In esophagus longitudinal muscle and gastric fundus, EFS evoked cholinergically mediated, monophasic contractions, attenuated by simultaneous nitrergic activation. Motilin (100-300 nM) reduced esophagus circular muscle contractions during EFS, unaffected by L-NAME or apamin. Motilin 300 nM also reduced EFS-evoked contractions of longitudinal muscle. Similar concentrations of motilin facilitated cholinergic activity in the fundus and increased baseline muscle tension. Prucalopride facilitated EFS-evoked contractions in esophagus (tested at 30 μM) and fundus (0.1-30 μM). Selective motilin and 5-HT₄ agonists have different, region-dependent abilities to modulate human esophageal and stomach neuromuscular activity, exemplified by weak inhibition (motilin) or excitation (5-HT₄) in esophageal body and excitation for both in stomach. In different patients with motility dysfunctions, motilin and 5-HT₄ agonists may reduce gastro-esophageal reflux in different ways.