PRESERVATION OF 5-HYDROXYTRYPTAMINE1A RECEPTOR G-PROTEIN INTERACTIONS IN THE CEREBRAL-CORTEX OF PATIENTS WITH ALZHEIMERS-DISEASE

The coupling of 5-hydroxytryptamine1A (5-HT1A) receptors to guanine nucleotide binding (G) proteins was investigated in membranes prepared from frontal and parietal cortices of control and Alzheimer's disease brains by characterising the effect of guanosine 5'-[beta-gamma-imido]diphosphate (Gpp[NH]p) on [H-3]8-hydroxy-2-(di-n-propylamino)-tetralin ([H-3]8-OH-DPAT) binding parameters. In the absence of guanine nucleotides, [H-3]8-OH-DPAT bound to a single high affinity binding site in all membrane types. The number of [H-3]8-OH-DPAT binding sites was significantly decreased in the parietal cortex of Alzheimer's disease samples compared with controls, whereas in the frontal cortex the number of binding sites remained unchanged. Gpp[NH]p reduced the [H-3]8-OH-DPAT binding affinity and the number of binding sites to the same degree in both regions in control and Alzheimer's disease cases. [H-3]8-OH-DPAT binding was inhibited in a concentration dependent manner with an IC50 value of approximately 1-mu-M in all cases. These results suggest that the 5-HT1A receptor-G protein complex is functionally intact in these regions in Alzheimer's disease brain.