Mu and kappa opiate binding sites in the rabbit CNS

We have examined the ability of various opiates to compete with the binding of 3H-etorphine (0.5 nM) in membranes from the rabbit cerebellum and thalamus. Our data suggest that greater than 80% of 3H-etorphine binding occurs at mu receptor sites in cerebellum membranes. In thalamus membranes, D-Ala2, D-Leu5-enkephalin (DADL) resolves binding of 3H-etorphine into two components. The first component accounts for about 50% of binding and may represent interaction of the radioligand with mu receptor sites. The second component is unaffected in the presence of high (1-5 microM) concentrations of DADL. The ranking of potency for opiate inhibition of the second component is ethylketocyclazocine greater than naloxone much greater than morphine much greater than DADL, suggesting it represents binding of 3H-etorphine to a kappa-opiate binding site. In the rabbit brain, the kappa-opiate binding site is particularly abundant in the thalamus followed by frontal cortex and caudate nucleus.