LIGAND-BINDING PROFILES OF U-69,593-SENSITIVE AND U-69,593-INSENSITIVE SITES IN HUMAN CEREBRAL-CORTEX MEMBRANES - EVIDENCE OF KAPPA-OPIOID RECEPTORS HETEROGENEITY

Receptor binding studies were performed to characterize the properties of subtypes of kappa opioid receptors in membrane preparations of hum an cerebral cortex. [H-3]U69,593 ([H-3]U69), a selective kappa(1)-agon ist, and [H-3]diprenorphine ([H-3]DIP), a non-selective opioid antagon ist, in the presence of 1 mu M each of DAMGO, DPDPE and U-69 to block mu-, gamma-, and kappa(1)-sites, labeled single population of binding sites, respectively. [H-3]U-69 binding sites (Kd = 3.8 +/- 0.2 nM, Bma x = 6.3 +/- 0.2 fmol/mg protein) had a binding profile that correspond to kappa(1)-receptor. That is, dynorphin A (1-13) (Dyn A), bremazocin e (BZC), U50,488H (U50), (-)ethylketocyclazocine (EKC) and nor-binalto rphimine (nor-BNI) bound to this site with high affinities. [H-3]DIP l abeled binding sites (Kd = 7.3 +/- 0.2 nM, Bmax = 102 +/- 9 fmol/mg pr otein) that were not sensitive to U-50, but to BZC, EKC and nor-BNI. T hese results indicate that kappa(1) and kappa(2) opioid receptors exis t in human cerebral cortex with different ligand binding profiles.