Enteric inhibitory neural regulation of human colonic circular muscle: role of nitric oxide

Gastroenterology. 1993 Oct;105(4):1009-16. doi: 10.1016/0016-5085(93)90943-7.


Background: Nitric oxide and an apamin-sensitive transmitter may both contribute to neural inhibition in the human colon. The present study investigated the role of NO in regulating spontaneous rhythmic contractions and examined NO-dependent and independent components of neurally evoked hyperpolarization in the human colon.

Methods: Mechanical and electrical activity were recorded from isolated circular muscle strips.

Results: Rhythmic contractions were inhibited by nerve stimulation. This response was reduced by apamin, oxyhemoglobin, and L-NG-nitro arginine methyl ester (L-NAME). Electrical recording revealed two components of neurally evoked hyperpolarization: a fast hyperpolarization resulting from a single stimulus and a sustained hyperpolarization that developed with repetitive stimulation. Fast hyperpolarization was not affected by L-NAME or oxyhemoglobin but was significantly reduced by apamin. The sustained hyperpolarization was reduced by L-NAME or apamin. Exogenous NO and the P2y receptor agonist 2-methylthio adenosine 5'-triphosphate (2-MATP) inhibited spontaneous contractions and produced hyperpolarization. Apamin reduced the effects of 2-MATP but not those of NO.

Conclusions: The results support the concept that the inhibitory neurotransmission in the human colon involves two transmitters. A single stimulus results in an apamin-sensitive response. With multiple stimuli, a NO-dependent response develops and sums with the apamin-sensitive mechanism, producing sustained hyperpolarization and inhibition of contractions.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Action Potentials / physiology
  • Adenosine Triphosphate / analogs & derivatives
  • Adenosine Triphosphate / pharmacology
  • Apamin / pharmacology
  • Arginine / analogs & derivatives
  • Arginine / pharmacology
  • Colon / innervation
  • Colon / physiology*
  • Electrophysiology
  • Humans
  • Muscle Contraction / physiology*
  • Muscle, Smooth / innervation
  • Muscle, Smooth / physiology*
  • NG-Nitroarginine Methyl Ester
  • Neurons / physiology*
  • Neurotransmitter Agents / pharmacology
  • Nitric Oxide / physiology*
  • Oxyhemoglobins / pharmacology
  • Synaptic Transmission / physiology
  • Thionucleotides / pharmacology


  • Neurotransmitter Agents
  • Oxyhemoglobins
  • Thionucleotides
  • Apamin
  • Nitric Oxide
  • Adenosine Triphosphate
  • Arginine
  • NG-Nitroarginine Methyl Ester
  • 2-methylthio-ATP