Disrupted beta 1-adrenoceptor-G protein coupling in the temporal cortex of patients with Alzheimer's disease.
The efficacy of beta 1-adrenoceptor-G protein coupling was studied in postmortem temporal cortex synaptic membranes from a series of control and Alzheimer's disease subjects. For the control cases, the non-hydrolysable GTP analogue 5'-guanylylimidodiphosphate (Gpp[NH]p) gave a significant reduction in the affinity of the agonist isoprenaline to displace binding of the radiolabelled antagonist (+/)-4-(3-t-butylamino-2-hydroxypropoxy)[5,7-3H]benzimidazol-2-one ([3H]CGP-12177). This effect was attributed to the conversion of high agonist-affinity sites to a lower-affinity state and was not found for the Alzheimer's disease cases. These data indicate that a disruption of beta 1-adrenoceptor-G protein coupling occurs in the temporal cortex of Alzheimer's disease patients.
Department of Geriatric Medicine, Karolinska Institute, Huddinge University Hospital, Sweden.
R F
RF
Cowburn
M
M
Vestling
C J
CJ
Fowler
R
R
Ravid
B
B
Winblad
C
C
O'Neill
D000368:Aged; D000544:Alzheimer Disease / Q000378:metabolism*; D001667:Binding, Competitive; D005260:Female; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D006801:Humans; D007545:Isoproterenol / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D011412:Propanolamines / Q000378:metabolism / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013570:Synaptic Membranes / Q000378:metabolism*; D013702:Temporal Lobe / Q000378:metabolism*
D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; D006165:Guanylyl Imidodiphosphate; C026777:ICI 118551; D019204:GTP-Binding Proteins; D007545:Isoproterenol; C033394:CGP 12177