Opioid binding sites of the κ-type in guinea-pig cerebellum

Abstract

(−)-[ 3H]Bremazocine interacts almost equally well with the μ-, δ- and κ-types of opioid binding sites. In homogenates of guinea-pig cerebellum, it was bound with high affinity (K D = 0.046 nM) and the maximum binding capacity was 7.04 pmol/g wet wt of tissue. When the μ- and δ-binding of (−)-[ 3H]bremazocine was prevented with unlabelled ligands, aK D of 0.034 nM and a capacity of 5.94 pmol/g tissue was found for the κ-binding site, which therefore comprised 84% of the opioid binding sites in the cerebellum. Autoradiographic analysis showed that the binding of (−)-[ 3H]bremazocine was relatively low in lobules IX and X and that it was predominantly located in the molecular and to a lesser extent in the granular layers. The addition of unlabelled μ- and δ-ligands did not alter the distribution. Thus, the guinea-pig cerebellum contains opioid binding sites of which almost all are of the κ-type and is therefore an ideal tissue for the isolation of κ-receptors and for the investigation of their biochemical and pharmacological properties.