Classification of multiple morphine and enkephalin binding sites in the central nervous system.
Detailed competitive displacement curves of 3H-labeled [D-Ala2,Met5]enkephalinamide, [D-Ala2,D-Leu5]enkephalin, and dihydromorphine by a series of opiates and enkephalins are biphasic, suggesting multiple sites. After treatment of tissue with naloxazone, the displacement of the three 3H-labeled ligands by all opiates and enkephalins tested becomes monophasic, losing the high-affinity displacement seen with low concentrations of both opiates and enkephalins. Coupled with Scatchard analysis of saturation experiments, these findings suggest a common site that binds both opiates and enkephalins equally well and with highest affinity (Kd values, less than 1 nM). Termed the mu 1 site, it corresponds to the previously described high-affinity site and appears to be the site responsible for analgesia under normal circumstances. The low-affinity binding of [3H]dihydromorphine (Kd, 3 nM) remaining after naloxazone treatment differs dramatically from low-affinity [D-Ala2,D-Leu5]-[3H]enkephalin binding (Kd, 5 nM). The mu 2 site, corresponding to the low-affinity [3H]dihydromorphine receptor sites, binds morphine (Ki, 10 nM) and dihydromorphine (Kd, 3 nM) far better than [D-Ala2,D-Leu5]enkephalin (Ki, 50 nM). Low-affinity [D-Ala2,D-Leu5]-[3H]enkephalin receptor sites bind [D-Ala2,D-Leu5]enkephalin (Ki, 5-8 nM) more potently than morphine (Ki, 71 nM) and correspond to the previously established delta receptor.
D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D004723:Endorphins / Q000378:metabolism*; D004744:Enkephalin, Methionine / Q000031:analogs & derivatives*; D004745:Enkephalins / Q000378:metabolism*; D007700:Kinetics; D009020:Morphine / Q000378:metabolism*; D009270:Naloxone / Q000378:metabolism; D051381:Rats; D011957:Receptors, Opioid / Q000378:metabolism*; D013329:Structure-Activity Relationship
D004723:Endorphins; D004745:Enkephalins; D011957:Receptors, Opioid; D009270:Naloxone; D004744:Enkephalin, Methionine; C022118:enkephalinamide-Met, Ala(2)-; D009020:Morphine