COUPLING OF HUMAN BRAIN CEREBRAL CORTICAL ALPHA-2-ADRENOCEPTORS TO GTP-BINDING PROTEINS IN ALZHEIMERS-DISEASE

The coupling of alpha-2-adrenoceptors to guanine nucleotide binding G-proteins was investigated in cerebral cortical membranes from control and Alzheimer's disease brain by characterizing the effects of MnCl2 and Gpp[NH]p on [H-3]clonidine binding. The manganese induced elevation of [H-3]clonidine binding was apparent in both control and Alzheimer's disease samples and the effect showed no significant difference between the two groups in the frontal cortex. However, the MnCl2 concentration dependence curves for control and Alzheimer's disease samples were significantly different from one another in the temporal cortex, whereas the pattern of stimulation by MnCl2 remained the same. The guanine nucleotide analogue, Gpp[NH]p inhibited [H-3]clonidine binding in a concentration-dependent manner, the profiles of inhibition showing no significant differences between control and Alzheimer's disease samples. Analysis of the effect of Gpp[NH]p on [H-3]clonidine saturation binding curves showed no significant differences between control and Alzheimer's disease samples in either frontal (K(d) = 9.68 +/- 1.38, 9.1 +/- 2.6 nM; B(max) = 40.23 +/- 4.33, 44.3 +/- 9.4 fmol/mg, control and Alzheimer's disease values, respectively), or temporal (K(d) = 11.61 +/- 4.04, 5.38 +/- 2.5 nM; B(max) = 52.0 +/- 14.0, 31.07 +/- 8.00 fmol/mg control and Alzheimer's disease values, respectively) cortices. [H-3]Clonidine binding parameters, measured in the presence of manganese were significantly different in the temporal cortex in Alzheimer's disease compared to control samples, (K(d) = 0.53 +/- 0.06, 1.02 +/- 0.16 nM; B(max) = 46.22 +/- 2.58, 82.41 +/- 5.48 fmol/mg, control and Alzheimer's disease values, respectively), whereas in the frontal cortex binding parameters, in the presence of manganese, remained the same between groups (K(d) = 0.61 +/- 0.05, 0.64 +/- 0.11 nM; B(max) = 52.35 +/- 2.0, 50.50 +/- 4.27 fmol/mg, control and Alzheimer's disease values, respectively). It is concluded that there are no gross disturbances in the alpha-2-adrenoceptor-G-protein complex in Alzheimer's disease brain.