Pharmacological properties of a proenkephalin A-derived opioid peptide: BAM 18.
BAM 18 is a derivative of the opioid precursor proenkephalin A. Although it exists in rat and guinea-pig brain in relatively high concentrations, its physiological function is presently unknown. In the present study we have determined the opioid receptor selectivity of this peptide using radioligand binding and peripheral tissue bioassay. When selective binding conditions were used, BAM 18 bound to the mu opioid receptor with an affinity three times that of the kappa opioid receptor and over 10 times that of the delta opioid receptors (Ki = 0.29, 0.75, and 3.2 nM respectively). BAM 18 also displayed mixed receptor selectivity in in vitro bioassay. Ke values for naloxone antagonism of BAM 18 agonist activity in the electrically stimulated guinea-pig ileum and the mouse vas deferens were 4.3 and 9.9 nM, respectively. These data indicate that BAM 18 binds to all three opioid receptor subtypes with a selectivity profile of mu greater than kappa greater than delta.
D000818:Animals; D001681:Biological Assay; D004305:Dose-Response Relationship, Drug; D004723:Endorphins / Q000378:metabolism / Q000494:pharmacology*; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives / Q000378:metabolism; D016308:Enkephalin, Leucine-2-Alanine; D004744:Enkephalin, Methionine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D004745:Enkephalins / Q000378:metabolism*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007930:Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D011498:Protein Precursors / Q000378:metabolism* / Q000494:pharmacology*; D011869:Radioligand Assay; D011957:Receptors, Opioid / Q000187:drug effects; D013329:Structure-Activity Relationship
D004723:Endorphins; D004745:Enkephalins; D011498:Protein Precursors; D011957:Receptors, Opioid; C029992:proenkephalin; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; C053492:BAM 18P; D009270:Naloxone; D004744:Enkephalin, Methionine; D004743:Enkephalin, Leucine; D016308:Enkephalin, Leucine-2-Alanine; D007930:Leucine; C012211:ubenimex