Preservation of 5-hydroxytryptamine1A receptor-G protein interactions in the cerebral cortex of patients with Alzheimer's 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 [3H]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 IC50 value of approximately 1 microM 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.
O'Neill
C
C
Alzheimer's Disease Research Centre, Karolinska Institute, Department of Geriatric Medicine, Huddinge University Hospital, Sweden.
Cowburn
R F
RF
Wiehager
B
B
Alafuzoff
I
I
Winblad
B
B
Fowler
C J
CJ
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000368:Aged; D000544:Alzheimer Disease / Q000378:metabolism*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006150:Guanine Nucleotides / Q000494:pharmacology; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D006651:Histocytochemistry; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D016612:Paraffin Embedding; D010296:Parietal Lobe / Q000187:drug effects / Q000378:metabolism; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013764:Tetrahydronaphthalenes / Q000378:metabolism
D006150:Guanine Nucleotides; D011985:Receptors, Serotonin; D013764:Tetrahydronaphthalenes; D006165:Guanylyl Imidodiphosphate; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D019204:GTP-Binding Proteins