Premium
Regionally dependent neuromuscular functions of motilin and 5‐ HT 4 receptors in human isolated esophageal body and gastric fundus
Author(s) -
Broad J.,
Hughes F.,
ChinAleong J.,
Sifrim D.,
Sanger G. J.
Publication year - 2014
Publication title -
neurogastroenterology and motility
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.489
H-Index - 105
eISSN - 1365-2982
pISSN - 1350-1925
DOI - 10.1111/nmo.12394
Subject(s) - motilin , medicine , endocrinology , cholinergic , contraction (grammar) , esophagus , stomach , muscle contraction , atropine , acetylcholine , neuromuscular transmission , biology
Background Motilin agonists promote human gastric motility and cholinergic activity, but excitatory and inhibitory actions are reported in the esophagus. The effect of 5‐ HT 4 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‐ HT 4 receptor agonists, modulate neuromuscular functions in human esophagus and gastric fundus. Methods Electrical field stimulation ( EFS ) evoked nerve‐mediated contractions of circular and longitudinal muscle from human esophageal body and circular muscle from gastric fundus. Key Results 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). Conclusions & Inferences Selective motilin and 5‐ HT 4 agonists have different, region‐dependent abilities to modulate human esophageal and stomach neuromuscular activity, exemplified by weak inhibition (motilin) or excitation (5‐ HT 4 ) in esophageal body and excitation for both in stomach. In different patients with motility dysfunctions, motilin and 5‐ HT 4 agonists may reduce gastro‐esophageal reflux in different ways.