title: Further demonstration of kappa opioid binding sites in the brain: evidence for heterogeneity.
abstract: By selectively blocking cross-interferences from other types of binding sites, a binding site which likely represents kappa opioid binding sites was obtained in the guinea-pig brain suspension of the particulate fraction. Selective ligands for mu, sigma, delta and epsilon opioid binding sites were poor inhibitors for inhibiting [3H]ethylketocyclazocine binding to this site, whereas kappa opioids like oxilorphan, dynorphin(1-13), ethylketocyclazocine, butorphanol, cyclazocine, ketocyclazocine, tifluadom, nalorphine, pentazocine, U-50-488, nalbuphine and naloxone were potent ligands. Buprenorphine, generally believed to be a mu opiate, was the most potent inhibitor at the kappa site. Scatchard analysis of the saturation curve of [3H]ethylketocyclazocine binding revealed two subtypes of kappa binding sites: a high-affinity site and a low-affinity site with Kd = 0.7 and 78 nM and maximum binding = 22 and 101 fmol/mg of protein, respectively. Analysis of the inhibition curves suggested that tifluadom may be a selective ligand for the high-affinity site and that dynorphin(1-13) and U-50-488 may bind preferentially the high-affinity site but still possess appreciable affinity for the low-affinity site. This study demonstrates a selective assay for kappa opioid binding sites and indicates a possibility of the heterogeneity of kappa opioid binding sites in the brain.
authors.forename: T P
authors.initials: TP
authors.lastname: Su
mesh_terms: D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000818:Animals; D001569:Benzodiazepines / Q000378:metabolism; D001665:Binding Sites; D001921:Brain / Q000378:metabolism*; D003496:Cyclazocine / Q000031:analogs & derivatives / Q000378:metabolism; D004399:Dynorphins / Q000378:metabolism; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives / Q000378:metabolism; D016308:Enkephalin, Leucine-2-Alanine; D016314:Ethylketocyclazocine; D005048:Etorphine / Q000378:metabolism; D006168:Guinea Pigs; D007977:Levallorphan / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D011759:Pyrrolidines / Q000378:metabolism; D011957:Receptors, Opioid / Q000378:metabolism*; D017473:Receptors, Opioid, kappa; D013237:Stereoisomerism
chemical_list: D010446:Peptide Fragments; D011759:Pyrrolidines; D011957:Receptors, Opioid; D017473:Receptors, Opioid, kappa; D001569:Benzodiazepines; D007977:Levallorphan; D005048:Etorphine; C044130:dextrallorphan; D016314:Ethylketocyclazocine; D004743:Enkephalin, Leucine; D016308:Enkephalin, Leucine-2-Alanine; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; C026843:dynorphin (1-13); D004399:Dynorphins; D003496:Cyclazocine; C035470:tifluadom