Further Demonstration of Kappa Opioid Binding Sites in the Brain: Evidence for Heterogeneity

By selectively blocking cross-interferences from other types of binding sites, a binding site which likely represents kappa opiold 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 opiolds like oxilorphan, dynorphin(I-1 3), ethylketocyclazocine, butorphanol, cyclazocane, ketocydazocine, tifluadom, nalor-phine, 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]ethylketocydazocine bind-ing revealed two subtypes of kappa binding sites: a high-affinity site and a low-affinity site wfth K = 0.7 and 78 nM and maximum binding = 22 and 1 01 frnol/mg of protein, respectively. Analysi