Preservation of 5-hydroxytryptamine1A receptor-G protein interactions in the cerebral cortex of patients with Alzheimer's disease.

Abstract

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.

• Authors: C O'Neill, R F Cowburn, B Wiehager, I Alafuzoff, B Winblad, C J Fowler
• Journal: Neuroscience letters (Neurosci Lett) Vol. 133 Issue 1 Pg. 15-9 (Nov 25 1991) ISSN: 0304-3940 [Print] Ireland
• PMID: 1838799 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Guanine Nucleotides
• Receptors, Serotonin
• Tetrahydronaphthalenes
• Guanylyl Imidodiphosphate
• 8-Hydroxy-2-(di-n-propylamino)tetralin
• GTP-Binding Proteins

Topics

• 8-Hydroxy-2-(di-n-propylamino)tetralin
• Aged
• Alzheimer Disease (metabolism)
• Cerebral Cortex (drug effects, metabolism)
• Female
• Frontal Lobe (drug effects, metabolism)
• GTP-Binding Proteins (metabolism)
• Guanine Nucleotides (pharmacology)
• Guanylyl Imidodiphosphate (pharmacology)
• Histocytochemistry
• Humans
• In Vitro Techniques
• Male
• Paraffin Embedding
• Parietal Lobe (drug effects, metabolism)
• Receptors, Serotonin (drug effects, metabolism)
• Signal Transduction (drug effects)
• Tetrahydronaphthalenes (metabolism)