Differential effect of humoral endorphin on the binding of opiate agonists and antagonists.
Humoral (H) endorphin, a novel endogenous factor with opiate-like activity was further characterized using various radioreceptor assays. H-Endorphin displaced both labelled opiates (morphine, ethylketazocine) and opioid peptides (leucine-enkephalin) from their specific binding sites in rat brain membranes. The effect of sodium ions on H-endorphin indicates its agonistic nature which is in agreement with previous pharmacological experiments. However, H-endorphin potentiated the binding of the opiate antagonist naloxone to brain membranes. This peculiar effect of H-endorphin on naloxone, together with the non-conventional interactions observed in various pharmacological assays, clearly distinguishes H-endorphin from other opioid ligands. A multisite model of the opiate receptor is presented. This model, which is compatible with the well documented evidence for receptors heterogeneity also explains non-conventional interactions between various opioid ligands.
D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D003496:Cyclazocine / Q000031:analogs & derivatives / Q000378:metabolism; D004723:Endorphins / Q000494:pharmacology*; D004745:Enkephalins / Q000378:metabolism; D016314:Ethylketocyclazocine; D066298:In Vitro Techniques; D008297:Male; D009020:Morphine / Q000378:metabolism; D009270:Naloxone / Q000378:metabolism; D009292:Narcotic Antagonists / Q000378:metabolism*; D009294:Narcotics / Q000378:metabolism*; D011813:Quinuclidinyl Benzilate / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats; D011957:Receptors, Opioid / Q000187:drug effects / Q000378:metabolism*; D012964:Sodium / Q000494:pharmacology
D004723:Endorphins; D004745:Enkephalins; D009292:Narcotic Antagonists; D009294:Narcotics; D011957:Receptors, Opioid; D009270:Naloxone; D016314:Ethylketocyclazocine; D011813:Quinuclidinyl Benzilate; D009020:Morphine; C028986:endorphin, humoral; D012964:Sodium; D003496:Cyclazocine