Binding and metabolism studies with [3H](D-Ala2,Leu5)enkephalinamide and [3H](D-Ala2,Pro5)enkephalinamide: evidence for a selective interaction of (D-Ala2,Pro5)enkephalinamide with mu-receptors.
We have compared the binding characteristics of [3H](D-Ala2,Leu5)enkephalinamide and [3H](D-Ala2,Pro5)enkephalinamide on a washed homogenate from mouse brain. The maximum number of binding sites for [3H](D-Ala2,Leu5)enkephalinamide was twice that obtained with [3H](D-Ala2,Pro5)enkephalinamide. Hill slopes of the displacement curves for opiates and (D-Ala2,Pro5)enkephalinamide obtained against [3H](D-Ala2,Leu5)enkephalinamide were considerably lower than that of (D-Ala2,Met5)enkephalinamide and (D-Ala2,Leu5)enkephalinamide. In contrast, Hill slopes for morphine, ketocyclazocine and (D-Ala2,Leu5)enkephalinamide were similar for the displacement of [3H](D-Ala2,Pro5)enkephalinamide. These results are discussed and interpreted in terms of a selective interaction for (D-Ala2,Pro5)enkephalinamide with mu-receptors and a similar affinity of (D-Ala2,Leu5)enkephalinamide for mu- and delta-receptors. Since metabolism studies did not show any difference in the degradation rate of these two enkephalin analogs, the discrepancy between in vitro and in vivo activity cannot result from the catabolism processes. Another possible explanation is proposed.
D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism; D010450:Endopeptidases / Q000378:metabolism; D004723:Endorphins / Q000378:metabolism*; D016308:Enkephalin, Leucine-2-Alanine / Q000031:analogs & derivatives*; D004745:Enkephalins / Q000378:metabolism*; D007082:Ileum / Q000378:metabolism; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D008566:Membranes / Q000378:metabolism; D051379:Mice; D009294:Narcotics / Q000378:metabolism; D015260:Neprilysin; D010447:Peptide Hydrolases / Q000378:metabolism; D011957:Receptors, Opioid / Q000378:metabolism*; D017450:Receptors, Opioid, mu
D004723:Endorphins; D004745:Enkephalins; D009294:Narcotics; D011957:Receptors, Opioid; D017450:Receptors, Opioid, mu; D016308:Enkephalin, Leucine-2-Alanine; C030279:enkephalinamide-Leu, Ala(2)-; C031289:enkephalin, Ala(2)-ProNH2(5)-; D010450:Endopeptidases; D010447:Peptide Hydrolases; D015260:Neprilysin