Hypotonicity-Induced Increase in Duodenal Mucosal Permeability Is Regulated by Cholinergic Receptors in Rats

The role of cholinergic receptors in the regulation of duodenal mucosal permeability in vivo is currently not fully described.

To elucidate the impact of nicotinic and muscarinic acetylcholine receptor signaling in response to luminal hypotonicity (50 mM NaCl) in the proximal small intestine of rat.

The effect on duodenal blood-to-lumen clearance of ⁵¹Cr-EDTA (i.e., mucosal permeability) and motility was studied in the absence and presence of nicotinic and muscarinic receptor agonists and antagonists, a sodium channel blocker (tetrodotoxin), and after bilateral cervical vagotomy.

Rats with duodenal contractions responded to luminal hypotonicity by substantial increase in intestinal permeability. This response was absent in animals given a non-selective nicotinic receptor antagonist (mecamylamine) or agonist (epibatidine). Pretreatment with tetrodotoxin reduced the increase in mucosal permeability in response to luminal hypotonicity. Further, the non-selective muscarinic receptor antagonist (atropine) and agonist (bethanechol) reduced the hypotonicity-induced increase in mucosal permeability, while vagotomy was without an effect, suggesting that local enteric reflexes dominate. Finally, neither stimulating nor blocking the α7-nicotinic receptor had any significant effects on duodenal permeability in response to luminal hypotonicity, suggesting that this receptor is not involved in regulation of duodenal permeability. The effect of the different drugs on mucosal permeability was similar to the effect observed for duodenal motility.

A complex enteric intramural excitatory neural reflex involving both nicotinic and muscarinic receptor subtypes mediates an increase in mucosal permeability induced by luminal hypotonicity.