Proenkephalin A-derived peptide E and its fragments alter opioid contractility in the small intestine.

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.