The binding of kappa- and sigma-opiates in rat brain.
Detailed displacements of [3H]dihydromorphine by ketocyclazocine and SKF 10,047, [3H]ethylketocyclazocine by SKF 10,047, and [3H]SKF 10,047 by ketocyclazocine are all multiphasic, suggesting multiple binding sites. After treating brain tissue in vitro with naloxazone, all displacements lose the initial inhibition of 3H-ligand binding by low concentrations of unlabeled drugs. Together with Scatchard analysis of saturation experiments, these studies suggest a common site which binds mu-, kappa, and sigma-opiates and enkephalins equally well and with highest affinity (KD less than 1 nM). The ability of unlabeled drugs to displace the low affinity binding of [3H]dihydromorphine (KD = 3 nM), [3H]ethylketocyclazocine (KD = 4 nM), [3H]SKF 10,047 (KD = 6 nM), and D-Ala2-D-Leu5-[3H]enkephalin (KD = 5 nM) remaining after treating tissue with naloxazone demonstrates unique pharmacological profiles for each. These results suggest the existence of distinct binding sites for kappa- and sigma-opiates which differ from those sites which selectively bind morphine (mu) and enkephalin (delta).
D000818:Animals; D001665:Binding Sites; D001921:Brain / Q000378:metabolism*; D046508:Culture Techniques; D003496:Cyclazocine / Q000031:analogs & derivatives / Q000378:metabolism; D004090:Dihydromorphine / Q000378:metabolism; D004745:Enkephalins / Q000378:metabolism; D016314:Ethylketocyclazocine; D008024:Ligands / Q000378:metabolism; D008297:Male; D009270:Naloxone / Q000031:analogs & derivatives / Q000494:pharmacology; D009294:Narcotics / Q000378:metabolism*; D010620:Phenazocine / Q000031:analogs & derivatives / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000378:metabolism; D014316:Tritium
D004745:Enkephalins; D008024:Ligands; D009294:Narcotics; D011957:Receptors, Opioid; D014316:Tritium; D009270:Naloxone; D016314:Ethylketocyclazocine; C024224:naloxazone; C012134:SK&F 10047; D004090:Dihydromorphine; D010620:Phenazocine; D003496:Cyclazocine