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 μ and κ 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 μ and κ opiates. Compounds characterized on the basis of their pharmacological effects as κ opiates had DSR values between 0.3 and 2.2, regardless of their nature as agonists or antagonists. In contrast, the DSR for μ opiates ranged from 3.4 to 11. In rat brain membranes, UM 1382 (U-50, 488, a compound with pronounced κ 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.
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- Pharmacology, Toxicology and Pharmaceutics(all)