Effect of motilin on the lower oesophageal sphincter.

Abstract

SUMMARY The effect of motilin on lower oesophageal sphincter (LES) pressure has been studied in unanaesthetised specially trained dogs using an infusion manometric technique. Motilin produced significant rises in resting pressure and contractions of the LES after doses ranging from 0009 ug/kg to 0 05 jug/kg. Doses greater than 005 tg/kg resulted in repetitive high amplitude contractions. Atropine 30 ,ug/kg completely abolished the effect of the lower doses of motilin. Higher doses of motilin in atropinised dogs still caused a small rise in baseline pressure and contractile activity still appeared. Hexamethonium 2 mg/kg resulted in both a diminished rise in LES pressure and the disappearance of contractions after motilin. Hexamethonium and atropine together completely abolished the LES response to motilin. We conclude that motilin increases LES pressure by acting on preganglionic cholinergic neurones to release acetylcholine which excites other cholinergic neurones supplying the circular muscle of the LES.Alkalinisation of the duodenum stimulates motor activity of a denervated canine gastric fundal pouch (Brown et al., 1966). Crude duodenal extracts have the same action and recently Brown et al. (1971Brown et al. ( , 1973 have succeeded in isolating and identifying the complete amino acid sequence of the peptide responsible for this action. This substance, motilin, in a dose of 2,ug/kg intravenously results in a marked increase in both the frequency and strength of antral and fundal contractions.The lower oesophageal sphincter (LES)5 responds to all known gastrointestinal hormones (Cohen and Lipshutz, 1971;Thomas and Earlam, 1973). Purified natural porcine motilin induces phasic changes in LES pressure in anaesthetised dogs (Jennewein et al., 1975). This study was performed to evaluate the type and mechanism of action of motilin on the lower oesophageal sphincter in the unanaesthetised animal.

Effect of Atilmotin, a Motilin Receptor Agonist, on Esophageal, Lower Esophageal Sphincter, and Gastric Pressures

“…That increase in LES pressure occurred acutely (within 1–2 min); a similar result was seen in the present study. Other studies have shown that the increase in LES pressure due to motilin receptor agonists is cholinergically mediated [12, 13]. …”

Neurotensin-related regulation of the postprandial lower-oesophageal-sphincter pressure

“…This discrepancy might be explained by the possibility that NT is not the only regulatory peptide involved in the regulation of LESP. Motilin [6], for instance, may increase LESP; however, this peptide was not evaluated. Furthermore, the vegetative nervous system is also involved in LESP regulation.…”

“…Motilin increases the LESP [6], whereas vasoactive intestinal peptide (VIP) reduces the LESP [7]. Gastrin and cholecystokinin were initially thought to be important modulators of LESP but had significant effects only in pharmacological doses [8,9].…”

Pathophysiologie der gastroösophagealen Refluxkrankheit

“…Motilin bewirkt eine Erhöhung des Sphinkterruhedrucks [16], hingegen hat Neurotensin einen antagonistischen Effekt [17], Stö rungen der Neuroregulation über Mechanorezeptoren im KardiaFundus-Bereich sind auch verantwortlich für das vermehrte Auf treten von transienten Sphinkterrelaxationen im Rahmen der GERD [ 18,14], Auslösend sind dabei wahrscheinlich die erhöhten Druckverhältnisse im Kardiabereich bei Vorliegen einer Hiatus hernie.…”