Application of an irreversible opiate antagonist (beta-FNA, beta-funal-trexamine) to demonstrate dynorphin selectivity for K-opioid sites.
Application of 100 nM beta-FNA for 60 minutes to isolated longitudinal muscles-myenteric plexus preparations from the guinea pig ileum caused a marked antagonism of the inhibitory action of normorphine and leucine enkephalin without greatly affecting the inhibitory potency of dynorphin or ethylketocyclazocine. The interaction of beta-FNA with the normorphine (mu-opiate receptors) appears to be non-equilibrium. Pretreatment with beta-FNA caused a significant increase in the apparent naloxone dissociation constant for normorphine and leucine enkephalin but not for dynorphin or ethylketocyclazocine. The results lend further support to the hypothesis that normorphine and the enkephalins activate preferentially mu-opiate receptors on the ileum, whereas dynorphin interacts predominantly at k-opiate sites.
D000818:Animals; D001667:Binding, Competitive; D004305:Dose-Response Relationship, Drug; D004399:Dynorphins; D004558:Electric Stimulation; D004723:Endorphins / Q000378:metabolism*; D006168:Guinea Pigs; D009022:Morphine Derivatives / Q000378:metabolism; D009130:Muscle, Smooth / Q000378:metabolism; D009270:Naloxone / Q000031:analogs & derivatives* / Q000378:metabolism; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000494:pharmacology; D011957:Receptors, Opioid / Q000187:drug effects / Q000378:metabolism*; D013997:Time Factors
D004723:Endorphins; D009022:Morphine Derivatives; D011957:Receptors, Opioid; D009270:Naloxone; D009271:Naltrexone; C024524:beta-funaltrexamine; D004399:Dynorphins; C010616:normorphine