Enteric locus of action of prokinetics: ABT-229, motilin, and erythromycin

Sushil K. Sarna, Asensio Gonzalez, Robert P. Ryan

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

We investigated the in vivo and in vitro locus of actions of prokinetics: motilin, erythromycin, and ABT-229. The test substances were infused close intra-arterially in short segments of the jejunum in the intact conscious state. Each prokinetic acted on a presynaptic neuron and utilized at least one nicotinic synapse to stimulate circular muscle contractions. The final neurotransmitter at the neuroeffector junction was ACh. Motilin and erythromycin, but not ABT-229, also released nitric oxide. Each prokinetic utilized somewhat different subtyped of muscarinic, serotonergic, tachykininergic, and histaminergic receptors, except for the M3 receptor, which was common to all of them. In contrast, none of the prokinetics stimulated contractions in mucosa-free or mucosa-attached muscle strips, or rings, even though methacholine or electrical field stimulation induced phasic contractions in all of them. The prokinetics also did not release ACh in longitudinal muscle-myenteric plexus preparations. Each prokinetic, however, decreased the length of enzymatically dispersed single cells. In conclusion, each prokinetic may act on a different subset of presynaptic neurons that converge on the postsynaptic cholinergic and nonadrenergic noncholinergic motoneurons. The presynaptic neurons may be impaired in the muscle bath environment.

Original languageEnglish (US)
Pages (from-to)G744-G752
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume278
Issue number5 41-5
StatePublished - May 1 2000

Keywords

  • Constipation
  • Enteric nervous system
  • Gastric emptying
  • Gastroesophageal reflux
  • Intestinal transit
  • Smooth muscle

ASJC Scopus subject areas

  • Gastroenterology
  • Physiology
  • Physiology (medical)

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