Further demonstration of kappa opioid binding sites in the brain: evidence for heterogeneity
Su, T.P.
Journal of Pharmacology and Experimental Therapeutics 232(1): 144-148
1985
ISSN/ISBN: 0022-3565 PMID: 2856939 Document Number: 248484
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 k opioids like oxilorphan, dynorphin(1-13), ethylketocyclazocine, butorphanol, cyclazocine, ketocyclazocine, tifluadom, nalorphine, pentazocine, U-50-488 [trans-D-1-3-4-dichloro-N-methyl-N-2-1-pyrrolidinyl-cyclohexyl benzeneacetamide methanesulfonate] 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.