Effect of D-Alanine Methionine Enkephalin Amide on Ion Transport in Rabbit Ileum

testine and the use of opiates to treat diarrheal diseases suggests that enkephalins may affect intestinal ion transport. Using isolated rabbit ileal mucosa, we found that leucine enkephalin, methionine enkephalin, and D-Ala2-methionine enkephalin amide (D-Ala2-Met E) decreased the short circuit current (ISC) and potential difference although the effect ofD-Ala2-Met E was more pronounced and prolonged. D-Ala2-Met E increased net sodium (+1.27±0.5 pueq/cm2h), and chloride ab-sorption (+2.33±0.4), and increased tissue conduc-tance by 37%. Although the effect of enkephalin on ion transport is opposite that ofcyclic AMP, D-Ala2-Met E had no effect on basal or vasoactive intestinal poly-peptide-stimulated cyclic AMP levels. The effect of D-Ala2-Met E on ISC was blocked by naloxone, suggest-ing the involvement of specific opiate receptors. Tetrodotoxin completely blocked the decrease in ISC in-duced by D-Ala2-Met E but not by epinephrine, in-ferring that enkephalins are preganglionic neurotrans-mitters. The effect of D-Ala2-Met E on ISC was not blocked by phentolamine, haloperidol, or pretreat-ment of animals with 6-hydroxydopamine, suggesting that enkephalin does not affect the Isc by stimulating the release of a-adrenergic or dopaminergic agonists. D-Ala2-Met E also decreased the Is, in the presence of carbachol and bethanechol, indicating that enkephalin does not inhibit the release of acetylcholine. Further, up to 10,uM atropine had no effect on the ISC. These studies demonstrate that enkephalins stimulate intes-tinal ion transport and may do so by stimulating (or in-hibiting) the release of a nonadrenergic, noncholiner-gic neurotransmitter