Preservation of 5-hydroxytryptamine 1A receptor-G protein interactions in the cerebral cortex of patients with Alzheimer's disease

Abstract

The coupling of 5-hydroxytryptamine 1A (5-HT 1A) 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′-[βγ-imido]diphosphate (Gpp[NH]p) on [ 3 H]8- hydroxy-2-( di-n- propylamino)-tetralin ([ 3H]8-OH-DPAT) binding parameters. In the absence of guanine nucleotides, [ 3H]8-OH-DPAT bound to a single high affinity binding site in all membrane types. The number of [ 3H]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 [ 3H]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. [ 3H]8-OH-DPAT binding was inhibited in a concentration dependent manner with an IC 50 value of approximately 1 μM in all cases. These results suggest that the 5-HT 1A receptor-G protein complex is functionally intact in these regions in Alzheimer's disease brain.