INTERACTION OF OPIOID-PEPTIDES AND OTHER DRUGS WITH MULTIPLE KAPPA-RECEPTORS IN RAT AND HUMAN BRAIN - EVIDENCE FOR SPECIES-DIFFERENCES

Previous experiments resolved four kappa binding sites in guinea pig brain terMed kappa1a, kappa1b, kappa2a, and kappa2b. The present study was undertaken to examine the occurrence of kappa receptor subtypes in rat and human brain. [H-3]U69,593 and [H-3]bremazocine were used to label kappa1 and kappa2 binding sites. respectively, present in brain membranes depleted of mu and delta binding sites by pretreatment with the irreversible ligands, BIT and FIT. Low levels of [H-3]U69,593 binding precluded a detailed quantitative study of kappa1 binding sites in these species. Quantitative examination of [H-3]bremazocine binding resolved two kappa2 binding sites in both rat and human brain whose ligand selectivity patterns differed from that of the guinea pig. These observations suggest that there may be considerable variation in the ligand recognition site Of kappa receptor subtypes among mammalian species.