[D-Ala2, Met5]-Enkephalinamide: CNS-mediated inhibition of prostaglandin-stimulated intestinal fluid and ion transport in the rat

Francis L. Quito, David R Brown

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

The opioid peptide [D-Ala2, Met5]-enkephalinamide (DAMA), a non-selective opioid agonist, has previously been shown to inhibit cholera toxin-induced fluid accumulation in the rat and dog small intestine after its intracerebroventricular (ICV) administration. In the present study, we examined the time course of the antisecretory/proabsorptive effects of ICV DAMA on net fluid and ion transport across the rat jejunum in situ during intravenous prostaglandin E1 (PGE) infusion. Net water and NaCl absorption were measured using a standard dilution marker technique in a 15-20 cm segment of proximal jejunum in urethaneanesthetized Sprague-Dawley rats. Infusion of PGE (5 μg/kg-min) over a 2 hr period produced a decrease in fluid and ion absorption that plateaued to a steady-state within 60 min. DAMA (1 and 3 μg/rat) administered by ICV bolus 60 min after the start of PGE infusion inhibited significantly PGE-induced decreases in water and chloride absorption relative to saline-treated controls. These dose-related peptide effects were expressed 15 min after DAMA treatment and were approximately 30 min in duration; they were antagonized by naloxone (1 mg/kg, IV) given at the time of DAMA injection. These results indicate that low concentrations of DAMA administered into the central nervous system rapidly and effectively inhibit changes in intestinal transport induced by a blood-borne secretagogue through an interaction with opiate receptors.

Original languageEnglish (US)
Pages (from-to)1029-1033
Number of pages5
JournalPeptides
Volume8
Issue number6
DOIs
StatePublished - Jan 1 1987

Keywords

  • CNS site of action
  • Enkephalin
  • Ion transport
  • Jejunum
  • Opioid
  • Prostaglandin E
  • Rat
  • Secretion

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