Resolution in the receptor binding of putative mu and kappa opiates

Conditions for the stereospecific binding of 3H-ethylketocyclazocine and 3H-etorphine were established in membranes from rat and pigeon brain. In displacing the specific binding of the radiolabeled ligands, putative mu and kappa opiates displayed different sensitivity toward sodium. In membranes from both species, the ratio of the sodium responses exhibited by a given drug in displacing 3H-ethylketocyclazocine and 3H-etorphine, respectively, ("double sodium ratio" = DSR) distinguished between mu and kappa opiates. Compounds characterized on the basis of their pharmacological effects as kappa opiates had DSR values between 0.3 and 2.2, regardless of their nature as agonists or antagonists. In contrast, the DSR for mu opiates ranged from 3.4 to 11. In rat brain membranes, UM 1382 (U-50,488, a compound with pronounced kappa activity) exhibited a DSR of 0.3, while the corresponding value for morphine was 7.4. Dynorphin-(1-13) had a DSR of 1. Within each of the two groups, the simple sodium ratio continued to serve as an index for the agonist or antagonist property of the tested opiates.