Regulation of colonic propulsion by enteric excitatory and inhibitory neurotransmitters

A. E. Foxx-Orenstein, J. R. Grider

Research output: Contribution to journalArticle

67 Scopus citations

Abstract

The contribution of excitatory and inhibitory motor neurotransmitters to colonic propulsion was examined in isolated segments of guinea pig colon. Synthetic fecal pellets were inserted at the proximal end of the segment, and the velocity of pellet propulsion across a fixed distance was measured in the presence and absence of selective neurotransmitter antagonists. The control velocity (0.97 ± 0.02 mm/s) was inhibited in a concentration-dependent fashion by atropine and the neurokinin (NK)-2a antagonist MEN-10,376 [half- maximal inhibitory concentration (IC50), 1 μM; maximal inhibition, 98 ± 1%]. The NK-1 antagonist GR-82,334 (10 μM) also inhibited velocity by 65 ± 9%, consistent with involvement of acetylcholine, neurokinin A (NK-2 agonist), and substance P (NK-1 agonist) in the contractile components of the peristaltic reflex. Velocity was also inhibited in a concentration-dependent fashion by the nitric oxide synthase inhibitor N(G)-nitro-L-arginine (L-NNA; IC50, 1 μM; maximal inhibition, 96 ± 2%) and by the vasoactive intestinal peptide (VIP) antagonist VIP-(10-28) (IC50, 30 nM; maximal inhibition, 64 ± 6%), consistent with involvement of both nitric oxide and VIP in descending relaxation of circular muscle and contraction of longitudinal muscle. A combination of threshold concentrations of L-NNA and the NK-2a antagonist was synergistic (53 ± 7% inhibition). The potentiation implied that the ascending and descending phases were functionally coupled in series. We conclude that blockade of neurotransmitters that mediate either phase of the peristaltic reflex inhibits colonic propulsive activity. Serial coupling of the phases leads to synergism between inhibitors, a condition of potential therapeutic importance.

Original languageEnglish (US)
Pages (from-to)G433-G437
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume271
Issue number3 34-3
StatePublished - Sep 1996

Keywords

  • enteric neurotransmitters
  • intestinal muscle
  • intestinal transit
  • nitric oxide
  • nitric oxide synthase
  • peristaltic reflex
  • tachykinin antagonists
  • vasoactive intestinal peptide

ASJC Scopus subject areas

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)

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