Motilin agonist erythromycin increases human lower esophageal sphincter pressure by stimulation of cholinergic nerves

Abstract

During phases II and III of the migrating motor complex, there is an increase in plasma motilin level that is synchronous with phasic and tonic contractile activity of the lower esophageal sphincter and of the stomach. The action of motilin on human lower esophageal sphincter is proposed to be mediated by cholinergic mechanisms. Recently, it has been shown that erythromycin was a motilin agonist. This study evaluated the pharmacological effects and the mechanisms of action of intravenous erythromycin on esophageal motility in humans. Healthy volunteers were studied three times at seven-day intervals in a randomized, double-blind fashion. Subjects were first studied for 10 min before drug administration. Afterwards, they received blindly and randomly an intravenous injection of placebo or atropine (12 micrograms/kg) followed by a 20-min continuous intravenous administration of placebo or erythromycin (150 mg). The difference (delta) between lower esophageal sphincter pressure and the duration, amplitude, and velocity of peristaltic contractions during the control period and after administration of drugs was compared. Erythromycin significantly increased (P < 0.05) the lower esophageal sphincter pressure (16.8 +/- 4.7 mm Hg) compared to placebo (-0.029 +/- 1.4 mm Hg). Erythromycin significantly decreased peristaltic contraction velocity compared to placebo (P < 0.05). The effects of erythromycin on lower esophageal sphincter pressure were completely blocked by previous administration of intravenous atropine. Erythromycin increased the number of fundic contractions compared to the placebo, but this effect was not blocked by the previous administration of atropine.(ABSTRACT TRUNCATED AT 250 WORDS)

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]. …”

Responses of human clasp and sling fibers to neuromimetics

“…Neural regulation comes mainly from the sympathetic and parasympathetic nerves, which exert their effects by affecting corresponding receptors including muscarinic, α‐ and β‐adrenergic, and DA receptors. A variety of foods, drugs and pathologic factors also influence the LES through these four receptors 15,16 . It has been demonstrated that the excitation of the vagus nerve plays an important role in the formation of the HPZ of the LES by controlling the release of Ach 17,18 .…”

Successful Symptomatic Management of a Patient with Ménétrier’s Disease with Long-Term Antibiotic Treatment

“…While a direct effect of both agents on enteric protein secretion cannot be definitely ruled out, it seems a highly unlikely explanation. Despite the fact that another macrolide antibiotic (erythromycin) has been reported to directly influence enteric motility [26, 27], to our knowledge no such data have been published for clarithromycin. In addition, no direct antisecretory properties of metronidazole have been described.…”