title: Proenkephalin A-derived peptide E and its fragments alter opioid contractility in the small intestine.
abstract: The human and canine small intestine exhibit increased contractility when exposed to exogenous or endogenous opioid peptides. The response of the canine small intestine to the proenkephalin A-derived peptide, peptide E and related processing fragments [Met5]enkephalin, BAM-12P, BAM-18P and BAM-22P was investigated by administering each peptide to isolated, small intestine segments which causes a significant increase in intraluminal pressure. Concentration-response curves from intraarterial bolus administration of peptide E, [Met5]enkephalin, BAM-12P, BAM-18P and BAM-22P showed decreasing efficacy with decreasing amino acid chain length while naloxone (305 nM) significantly antagonized the response. Results using the classical guinea pig ileum/myenteric plexus longitudinal muscle and mouse vas deferens bioassays with specific opioid receptor antagonists provide evidence that peptide E and BAM-18P are relatively specific to the mu opioid receptor, [Met5]enkephalin is more delta specific, BAM-22P is both mu and kappa specific and BAM-12P is kappa opioid receptor specific. These studies demonstrate that locally released (and possibly circulating) peptide E and related processing fragments increase contractility in the small intestine and may be active through more than a single receptor mechanism, particularly the mu receptor.
authors.affiliation: Department of Pharmacology, College of Medicine, University of Arizona, Tucson 85724.
authors.forename: T P
authors.initials: TP
authors.lastname: Davis
authors.forename: G L
authors.initials: GL
authors.lastname: Hoyer
authors.forename: P
authors.initials: P
authors.lastname: Davis
authors.forename: T F
authors.initials: TF
authors.lastname: Burks
mesh_terms: D000818:Animals; D004285:Dogs; D004744:Enkephalin, Methionine / Q000031:analogs & derivatives / Q000494:pharmacology; D004745:Enkephalins; D006168:Guinea Pigs; D006801:Humans; D066298:In Vitro Techniques; D007421:Intestine, Small / Q000187:drug effects; D008297:Male; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D009197:Myenteric Plexus / Q000187:drug effects; D010446:Peptide Fragments / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology*; D011498:Protein Precursors / Q000494:pharmacology; D014649:Vas Deferens / Q000187:drug effects
chemical_list: D004745:Enkephalins; D010446:Peptide Fragments; D010455:Peptides; D011498:Protein Precursors; C053492:BAM 18P; D004744:Enkephalin, Methionine; C026771:BAM 12P; C028837:BAM 22P; C039933:peptide E (adrenal medulla)