Article Text
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
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- 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