Nitrergic and purinergic mechanisms evoke inhibitory neuromuscular transmission in the human small intestine

Neurogastroenterol Motil. 2014 Mar;26(3):419-29. doi: 10.1111/nmo.12293. Epub 2013 Dec 25.

Abstract

Background: Inhibitory neuromuscular transmission in the human colon is due to nitrergic and purinergic (P2Y1 -mediated) inputs. The aim of this study was to determine the mechanisms of neuromuscular transmission in different regions of the human small intestine.

Methods: Ileal (n = 6) and jejunal (n = 6) samples underwent histological examination and were studied using sharp microelectrodes in smooth muscle cells and conventional muscle bath techniques. Electrical field stimulation (EFS) was used to stimulate inhibitory neurons.

Key results: No histological abnormalities were found. Resting membrane potential was -39.7 ± 1.5 and -45.5 ± 2.1 mV in the jejunum and ileum, respectively. Slow waves and spontaneous contractions were recorded at a frequency of about 8-9 and 6-7 cpm in the jejunum and ileum, respectively. In non-adrenergic, non-cholinergic conditions, EFS caused an inhibitory junction potential and mechanical relaxation. Both responses were blocked by tissue incubation with the nitric oxide synthase inhibitor (Nω-nitro-l-arginine 1 mM) and the P2Y1 receptor blocker 2'-deoxy-N(6) -methyladenosine 3',5'-bisphosphate tetrasodium salt (MRS2179; 10 μM). Both exogenous addition of sodium nitroprusside (1 μM) and the preferential P2Y1 receptor agonist ADPβS (1 μM) hyperpolarized and relaxed smooth muscle cells. MRS2179 (10 μM) blocked ADPβS-induced responses.

Conclusions & inferences: Similar to colon, inhibitory neurotransmission in the human small intestine is mainly mediated by purinergic (via P2Y1 receptors) and nitrergic inhibitory neurotransmission. Similar mechanisms of inhibitory neurotransmission are present in different regions of the human intestine.

Keywords: IJP; P2Y1 receptors; ileum; jejunum; purinergic.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Diphosphate / analogs & derivatives
  • Adenosine Diphosphate / pharmacology
  • Aged
  • Electric Stimulation
  • Enzyme Inhibitors / pharmacology
  • Female
  • Humans
  • Ileum / drug effects
  • Ileum / physiology*
  • Jejunum / drug effects
  • Jejunum / physiology*
  • Male
  • Middle Aged
  • Muscle, Smooth / drug effects
  • Muscle, Smooth / physiology
  • Neural Inhibition / drug effects
  • Neural Inhibition / physiology*
  • Neuromuscular Junction / drug effects
  • Neuromuscular Junction / physiology*
  • Nitric Oxide Donors / pharmacology
  • Nitroarginine / pharmacology
  • Nitroprusside / pharmacology
  • Purinergic P2Y Receptor Antagonists / pharmacology
  • Receptors, Purinergic P2Y1 / metabolism*
  • Thionucleotides / pharmacology

Substances

  • Enzyme Inhibitors
  • N(6)-methyl-2'-deoxyadenosine 3',5'-diphosphate
  • Nitric Oxide Donors
  • Purinergic P2Y Receptor Antagonists
  • Receptors, Purinergic P2Y1
  • Thionucleotides
  • Nitroprusside
  • Nitroarginine
  • adenosine 5'-O-(2-thiodiphosphate)
  • Adenosine Diphosphate