CHOLINERGIC MODULATION OF ELECTROGENIC ION-TRANSPORT IN DIFFERENT REGIONS OF THE RAT SMALL-INTESTINE

Acetylcholine acting via muscarinic receptors located in the intestina l mucosa controls ion and fluid transport. This study examined the pat hway(s) by which cholinergic receptors mediate secretion in rat isolat ed duodenum, jejunum and ileum using the short-circuit current (Isc) a s an index of electrogenic Cl- secretion. Carbachol and bethanechol in duced electrogenic Cl- transport which was insensitive to the neural b locker tetrodotoxin, indicating their direct action on the enterocytes . Functional characterization of electrogenic secretion activated via muscarinic receptors on jejunal and ileal enterocytes was achieved by use of selective muscarinic antagonists in the presence of tetrodotoxi n. In both regions the rank order of potency of these compounds (atrop ine >4-diphenylacetoxy-N-piperidine methiodide (4-DAMP) > hexahydro-si la-difenidol (HHSiD) >pirenzepine>methoctramine) indicated the M-3 rec eptor subtype. Secretion activated by the muscarinic agonist amino]car bonyl]-N,N,N-trimethyl-2-butyn-1-ammonium chloride (McN-A-343) was sen sitive to tetrodotoxin and pirenzepine but not to the ganglionic block er, hexamethonium, indicating the M-1 receptor subtype on post ganglio nic neurons. Regional differences for bethanechol-activated secretion showed an increasing gradient in secretory capacity (Isc max) in a pro ximal-to-distal direction along the small intestine. Responses to McN- A-343 also showed regional differences but these were unlike those of bethanechol. These results show that cholinomimetic-induced electrogen ic Cl- secretion in rat isolated small intestine appears to be mediate d by two dissimilar populations of muscarinic receptor: M-3 muscarinic receptors positioned on enterocytes and M-1 muscarinic receptors site d on submucosal neurons.