Coupling of muscarinic receptors to GTP proteins in postmortem human brain--alterations in Alzheimer's disease.
The coupling of muscarinic agonist receptors to guanine nucleotide-binding (G) proteins was investigated in the frontal, temporal cortices and thalamus of control and Alzheimer brains by using carbachol in competition experiments with [3H]QNB. In the presence of GppNHp, the carbachol/[3H]QNB competition binding data showed a 6-fold increase in the high-affinity muscarinic agonist coefficient (Ki high) in the thalami of control brains and a significantly increased proportion of low-affinity agonist binding sites (Bmax low) in the temporal cortices of control brains, while no significant effect of GppNHp was observed in Alzheimer brains. The results suggest a disturbance of the muscarinic receptor-G protein coupling in Alzheimer's disease.
Warpman
U
U
Department of Pharmacology, Uppsala University, Sweden.
Alafuzoff
I
I
Nordberg
A
A
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D001344:Autopsy; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002217:Carbachol / Q000494:pharmacology; D005260:Female; D005625:Frontal Lobe / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000032:analysis / Q000378:metabolism*; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D008297:Male; D011813:Quinuclidinyl Benzilate / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000032:analysis / Q000378:metabolism*; D012016:Reference Values; D013702:Temporal Lobe / Q000378:metabolism; D013788:Thalamus / Q000378:metabolism
D011976:Receptors, Muscarinic; D006165:Guanylyl Imidodiphosphate; D011813:Quinuclidinyl Benzilate; D002217:Carbachol; D019204:GTP-Binding Proteins