Effect of D-alanine methionine enkephalin amide on ion transport in rabbit ileum

J. Dobbins, L. Racusen, H. J. Binder

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The presence of enkephalins in the intestine and the use of opiates to treat diarrheal diseases suggests that enkephalins may affect intestinal ion transport. Using isolated rabbit ileal mucosa, the authors found that leucine enkephalin, methionine enkephalin, and D-Ala2-methionine enkephalin amide (D-Ala2-Met E) decreased the short circuit current [I(sc)] and potential difference although the effect of D-Ala2-Met E was more pronounced and prolonged. D-Ala2-Met E increased net sodium (+1.27 ± 0.5 μeq/cm2h), and chloride absorption (+2.33 ± 0.4), and increased tissue conductance by 37%. Although the effect of enkephalin on ion transport is opposite that of cyclic AMP, D-Ala2-Met E had no effect on basal or vasoactive intestinal polypeptide-stimulated cyclic AMP levels. The effect of D-Ala2-Met E on I(sc) was blocked by naloxone, suggesting the involvement of specific opiate receptors. Tetrodotoxin completely blocked the decrease in I(sc) induced by D-Ala2-Met E but not by epinephrine, inferring that enkephalins are preganglionic neurotransmitters. The effect of D-Ala2-Met E on I(sc) was not blocked by phentolamine, haloperidol, or pretreatment of animals with 6-hydroxydopamine, suggesting that enkephalin does not affect the I(sc) by stimulating the release of α-adrenergic or dopaminergic agonists. D-Ala2-Met E also decreased the I(sc) in the presence of carbachol and bethanechol, indicating that enkephalin does not inhibit the release of acetylcholine. Further, up to 10 μM atropine had no effect on the I(sc). These studies demonstrate that enkephalins stimulate intestinal ion transport and may do so by stimulating (or inhibiting) the release of a nonadrenergic, noncholinergic neurotransmitter.

Original languageEnglish (US)
Pages (from-to)19-28
Number of pages10
JournalJournal of Clinical Investigation
Issue number1
StatePublished - 1980
Externally publishedYes

ASJC Scopus subject areas

  • Medicine(all)


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