You are here

Article Text

Article menu
Download PDFPDF
Intestinal transport
Proabsorptive and prosecretory roles for nitric oxide in cholera toxin induced secretion
  1. J L Turvill,
  2. F H Mourad,
  3. M J G Farthing
  1. Digestive Diseases Research Centre, St Bartholomew’s and the Royal London School of Medicine and Dentistry, Turner Street, London E1 2AD, UK
  1. Dr J L Turvill.

Abstract

Background Cholera toxin causes small intestinal hypersecretion by inducing a coordinated response from enterocytes, enterochromaffin cells, enteric neurones, and the vascular supply. Nitric oxide has been implicated in the function of these separate components.

Aims To explore the role of nitric oxide in the totality of cholera toxin induced secretion in vivo.

Methods One group of adult male Wistar rats was treated with the nitric oxide synthase inhibitors NG-nitro-l-arginine methyl ester (l-NAME; subcutaneously or intraluminally), NG-methyl-l-arginine (l-NMA), or 7-nitroindazole. A second group of rats was treated withl-arginine (intraperitoneally or intraluminally) ord-arginine. The small intestine was isolated between two cannulae and instilled with 75 μg cholera toxin or saline for two hours. Small intestinal perfusion of a plasma electrolyte solution containing [14C]-PEG was undertaken to determine net water and electrolyte movement. After the experiment macroscopic and microscopic intestinal appearances were noted and jejunal 5-hydroxytryptamine concentrations were determined.

Results Both l-arginine and l-NAME induced secretion in the basal state, but only when administered intraluminally. Systemically appliedl-NAME caused a dose dependent reduction in cholera toxin induced secretion. This was paralleled by l-NMA but not by 7-nitroindazole or by intraluminally applied l-NAME. Systemically applied l-NAME caused notable cyanosis of the intestine, consistent with mesenteric ischaemia, but no microscopic abnormalities. Systemically applied l-arginine but notd-arginine also reduced cholera toxin induced secretion and inhibited 5-hydroxytryptamine release.

Conclusion Nitric oxide has a duality of roles in cholera toxin induced secretion, acting both as an absorbagogue and a secretagogue. Its mechanisms of action include the maintenance of mucosal perfusion and enterochromaffin cell stabilisation.

  • cholera toxin
  • nitric oxide
  • small intestinal transport
  • 5-hydroxytryptamine
  • l-arginine
  • nitric oxide synthase inhibitors

  • Abbreviations

    NO
    nitric oxide
    l-NAME
    NG-nitro-l-arginine methyl ester
    l-NMA
    NG-methyl-l-arginine
    cNOS
    constitutive nitric oxide synthase
    inducible nitric oxide synthase
    5-HT, 5-hydroxytryptamine
    PES
    plasma electrolyte solution
    PEG
    polyethylene glycol
    HPLC
    high performance liquid chromatography
    CT
    cholera toxin
    IQR
    interquartile range

    • https://doi.org/10.1136/gut.44.1.33

    Statistics from Altmetric.com

      Request Permissions

      If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

    • Abbreviations

      NO
      nitric oxide
      l-NAME
      NG-nitro-l-arginine methyl ester
      l-NMA
      NG-methyl-l-arginine
      cNOS
      constitutive nitric oxide synthase
      inducible nitric oxide synthase
      5-HT, 5-hydroxytryptamine
      PES
      plasma electrolyte solution
      PEG
      polyethylene glycol
      HPLC
      high performance liquid chromatography
      CT
      cholera toxin
      IQR
      interquartile range
      • View Full Text