Kappa-Opioid Receptor Binding Populations in Rhesus Monkey Brain: Relationship to an Assay of Thermal Antinociception

摘要: The binding characteristics of the kappa opioid ligands [3H]U69,593 and [3H]bremazocine, mu ligand [3H][D-ala2,N-Me-Phe4,glycol5]enkephalin delta [3H]p-Cl-[D-pen2,5]enkephalin were studied in rhesus monkey brain membranes saturation experiments followed by competition with a variety peptidic nonpeptidic ligands. sites appeared to be subset receptors (kappa-1 receptors: Kd, 1.2 nM; Bmax, 66 fmol/mg). [3H]Bremazocine (in presence receptor-masking agents), bound larger population (kappa-all: 0.39 227 fmol/mg), which presumably included aforementioned kappa-1 sites. Competition revealed that presently defined similar previously reported other mammalian species, particularly terms higher selectivity observed arylacetamide (e.g., U50,488) vs. benzomorphan agonists ethylketocyclazocine). kappa-selective antagonist norbinaltorphimine (nor-BNI) displayed very small (2.3-fold) for kappa-all This led prediction monkeys (n = 3), systemically administered nor-BNI (10 mg/kg s.c.) should have moderate degree antinociceptive effects putative kappa-1-agonist, U50,488 (0.1-3.2 s.c.), those agonist ethylketocyclazocine (0.01-056 s.c.). was confirmed vivo because mg/kg) caused robust long lasting (up 21 days) antagonism but significant ethylketocyclazocine. congener Cl-977 (enadoline), an 11-fold selectivity, not sensitive pretreatment. indicates subtype-binding profile is necessarily predictive its sensitivity vivo. Overall, present results suggest at least two functional receptor populations may brain.