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Nitric oxide-mediated contraction in enteric smooth muscle

L Barthó1, R A Lefebvre

  • 1Department of Pharmacology, University Medical School Pécs, Hungary.

Archives Internationales De Pharmacodynamie Et De Therapie
|January 1, 1995
PubMed
Summary

Nitric oxide (NO) causes both relaxation and contraction in gastrointestinal smooth muscle. Further research is needed to understand the mechanisms behind NO-induced contractions and their role in gut motility.

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Area of Science:

  • Gastroenterology
  • Neuroscience
  • Pharmacology

Background:

  • Nitric oxide (NO) is recognized as a neurotransmitter mediating nonadrenergic noncholinergic (NANC) smooth muscle relaxation in the gastrointestinal tract.
  • However, contractile responses to NO in gastrointestinal smooth muscle have also been documented, suggesting complex roles.

Purpose of the Study:

  • To investigate the dual effects of nitric oxide (NO) on gastrointestinal smooth muscle, specifically focusing on its contractile actions.
  • To elucidate the cellular mechanisms underlying NO-induced contractions in various segments of the gastrointestinal tract.

Main Methods:

  • Experiments utilized guinea-pig ileal longitudinal muscle-myenteric plexus preparations, opossum esophagus, and rat ileum models.
  • Pharmacological agents including tetrodotoxin, atropine, substance P antagonist, methylene blue, and nifedipine were employed to probe neuronal and cellular pathways.
  • Electrical field stimulation was used to investigate NANC nerve activity.

Main Results:

  • In guinea-pig ileum, NO induced relaxation followed by an aftercontraction mediated by cholinergic and tachykininergic neurons.
  • Primary contractions to NO were observed in rat ileum and opossum esophagus, occurring at lower concentrations than relaxant effects.
  • NO-induced contractions in rat ileum were independent of guanylate cyclase and cGMP but sensitive to L-type calcium channel blockers like nifedipine, indicating a role for extracellular calcium influx.

Conclusions:

  • Nitric oxide (NO) exhibits complex biphasic effects on gastrointestinal smooth muscle, including both relaxation and contraction.
  • NO-induced contractions may involve direct actions on smooth muscle cells, potentially through L-type calcium channels, and are distinct from its relaxant signaling pathways.
  • Understanding these dual roles is crucial for comprehending gastrointestinal motility regulation and potential therapeutic interventions.

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