PRESERVATION OF KAPPA(1) OPIOID RECEPTOR RECOGNITION SITE DENSITY ANDREGULATION BY G-PROTEINS IN THE TEMPORAL CORTEX OF PATIENTS WITH ALZHEIMERS-DISEASE

The pharmacological properties of the kappa(1) opioid receptor were in vestigated in human post-mortem temporal cortical membranes from contr ol and Alzheimer's disease brains, using the kappa(1)-selective radiol igand [H-3]U69593. [H-3]U69593 bound to a single high affinity site po pulation with no significant difference between control (B-max 31 +/- 4.14 fmol/mg protein, K-D 1.01 +/- 0.26 nM) and Alzheimer's disease br ains (B-max 37 +/- 4.63 fmol/mg protein, K-D 0.86 +/- 0.08 nM). Compet ition studies with dynorphin B and alpha-neoendorphin gave flat inhibi tion curves with Hill coefficients of 0.31 +/- 0.04 and 0.49 +/- 0.09 in the control brains and 0.38 +/- 0.05 and 0.48 +/- 0.08 in the Alzhe imer's disease brains, respectively. The pI(50) values for dynorphin B and alpha-neoendorphin were 8.73 +/- 0.17 and 8.48 +/- 0.09, respecti vely, in the control brains and 9.30 +/- 0.22 and 8.70 +/- 0.15 in the Alzheimer's disease brains. The guanine nucleotide analogue Gpp(NH)p inhibited binding by ca. 70% in both the control and Alzheimer's disea se brains, the residual binding being sensitive to NaCl in both cases. These results indicate that the pharmacological properties and the fu nctional integrity of G-protein coupling of the kappa(1) receptor reco gnition site are preserved in Alzheimer's disease temporal cortex.