Receptor-mediated activation of G proteins is reduced in postmortem brains from Alzheimer's disease patients.
The effects of Alzheimer's disease (AD) on [35S]GTP gamma S binding to G proteins was examined in postmortem cerebrocortex. Stimulation of the beta-adrenergic or muscarinic cholinergic receptors in control tissue with selective agonists resulted in increases in [35S]GTP gamma S binding to G alpha proteins in a receptor-specific fashion. The responses were markedly reduced in brain tissues from AD patients. In contrast, basal [35S]GTP gamma S binding to the G alpha proteins was relatively intact in AD brains. Immunoblot analyses reveal that levels of cerebrocortical G alpha proteins in AD are not altered. The results suggest that in AD the decrease in agonist-stimulated [35S]GTP gamma S binding to G proteins may be a result of decoupling between receptors and their associated G proteins.
Wang
H Y
HY
Department of Psychiatry, Medical College of Pennsylvania, Philadelphia 19129.
Friedman
E
E
D000368:Aged; D000544:Alzheimer Disease / Q000378:metabolism*; D001711:Biotransformation / Q000187:drug effects / Q000502:physiology; D001923:Brain Chemistry / Q000187:drug effects / Q000502:physiology*; D002217:Carbachol / Q000494:pharmacology; D005260:Female; D019204:GTP-Binding Proteins / Q000378:metabolism*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000493:pharmacokinetics; D006801:Humans; D015151:Immunoblotting; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D011485:Protein Binding; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000502:physiology*; D013462:Sulfur Radioisotopes
D017981:Receptors, Neurotransmitter; D013462:Sulfur Radioisotopes; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D002217:Carbachol; D019204:GTP-Binding Proteins; D007545:Isoproterenol