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Role of nitric oxide in intestinal water and electrolyte transport
  1. F H MOURAD
  1. J L TURVILL,
  2. M J G FARTHING
  1. Department of Medicine,
  2. American University of Beirut,
  3. Beirut, The Lebanon
  4. Digestive Diseases Research Centre,
  5. St Bartholomew’s and The Royal London
  6. School of Medicine and Dentistry,
  7. Turner Street, London E1 2AD, UK
  1. Dr Turvill.

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Since Palmer et al and Ignarroet al showed that vascular endothelial cells could synthesise nitric oxide (NO), this soluble gas has emerged as an important mediator, messenger and regulator of cell function in a number of physiological systems and pathophysiological states.1-4 The effect of NO on the intestinal epithelium, the local microcirculation, the enteric nervous system, and inflammatory cascades has implicated it as a potential mediator of intestinal water and electrolyte transport.5 Data produced by different groups over the past few years have been contradictory, some showing NO as an absorbagogue and others as a secretagogue.

Biology of nitric oxide and its source in the intestine

In biological systems, NO has a half life of less than 5 seconds, rapidly degrading to nitrite and nitrate in the presence of oxygen and water.1 Being soluble in both water and lipid, it freely traverses cell membranes and passes into adjacent target cells.6 The potential sources of NO in the gut are the endothelial cells, the intrinsic intestinal tissue (mast cells, epithelium, smooth muscle, neurones), residing and infiltrating leucocytes (neutrophils and monocytes), reduction of luminal gastric nitrates, and to a lesser extent denitrification by commensal intestinal bacteria.5 Nitric oxide is formed froml-arginine by the action of a stereospecific group of enzymes called nitric oxide synthases (NOS).7 In the gut, NOS have been localised in the myenteric and submucosal neurones in the subepithelial compartment and lamina propria including submucosal arterioles and venules, and in the apical epithelial cells.8-12 Nitric oxide can be produced by enterocytes through both the constitutive and the inducible NOS.13 ,14

Nitric oxide has been considered as a regulator of basal intestinal water transport, as a mediator of pathological conditions where disturbance in water transport plays a role, and as an effector substance in both laxatives and antidiarrhoeal agents. …

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