Neural control of colonic epithelial transport, motility and permeability in vivo. An experimental study in anaesthetized rats

Sammanfattning: Colonic dysfunction may result in diarrhoea, abdominal pain or constipation, andinflammatory bowel disease, bile acid malabsorption and particularly irritable bowelsyndrome are very common disorders. The role of the enteric nervous system (ENS) inthese diseases is largely unknown. Therefore, the purpose of this study was to investigatethe effects of enteric nerves on colonic epithelial transport, motility and permeabilityunder normal and bile acid exposed condition.The studies of colonic motility, transmural potential difference (PD), net fluid transportand permeability were carried out on the isolated proximal and distal rat colon with intactblood supply and innervation, mainly in vivo. 3H-mannitol and 14C-urea wereadministered i.v. as clearance probes. 4 mM decoxycholic acid (DCA) was put into thelumen to induce chemical irritation of the surface epithelium. The effects of the nerveblockers atropine, hexamethonium, lidocaine (applied onto the serosal surface) and thenitric oxide inhibitor Nw-nitro-L-arginine (L-NNA) were studied under control conditionsand during mucosal bile acid exposure.Muscarinic receptor blockade with atropine inhibited motor activity, had no significanteffect on net fluid transport and inhibited the bile acid induced increase in small solutepermeability. Nicotinic receptor blockade with hexamethonium abolished motor activity,enhanced electrically silent absorption in proximal colon, inhibited electrogenic secretionin distal colon and inhibited the bile acid induced permeability increase. Serosal lidocaineinduced colonic contractions, dissociated the normal linkage between contractions andsecretion, and inhibited the bile acid induced permeability increase in proximal colon.NO synthesis blockade with L-NNA potentiated the bile acid induced permeabilityincrease in distal colon.The data suggest that the ENS regulates not only colonic motility and secretion but alsocolonic permeability. The neural control of the colonic mucosa seems to be differentlyorganized from that of the small intestine. Instead of activating secretomotor neurons,chemical stimulation with bile acids leads to a largely neurally mediated increase incolonic permeability, a response that is in turn inhibited by nitric oxide. These resultssuggest that enteric nerves may play a pathophysiological role in the inflamed colonicmucosa. Pharmacological intervention with the neurally mediated permeability-regulatingsystem may be a new target for treatment of colonic secretomotor disorders.