Coupling of human brain cerebral cortical alpha 2-adrenoceptors to GTP-binding proteins in Alzheimer's disease.
The coupling of alpha 2-adrenoceptors to guanine nucleotide binding G-proteins was investigated in cerebral cortical membranes from control and Alzheimer's disease brain by characterizing the effects of MnCl2 and Gpp[NH]p on [3H]clonidine binding. The manganese induced elevation of [3H]clonidine binding was apparent in both control and Alzheimer's disease samples and the effect showed no significant difference between the two groups in the frontal cortex. However, the MnCl2 concentration dependence curves for control and Alzheimer's disease samples were significantly different from one another in the temporal cortex, whereas the pattern of stimulation by MnCl2 remained the same. The guanine nucleotide analogue, Gpp[NH]p inhibited [3H]clonidine binding in a concentration-dependent manner, the profiles of inhibition showing no significant differences between control and Alzheimer's disease samples. Analysis of the effect of Gpp[NH]p on [3H]clonidine saturation binding curves showed no significant differences between control and Alzheimer's disease samples in either frontal (Kd = 9.68 +/- 1.38, 9.1 +/- 2.6 nM; Bmax = 40.23 +/- 4.33, 44.3 +/- 9.4 fmol/mg, control and Alzheimer's disease values, respectively), or temporal (Kd = 11.61 +/- 4.04, 5.38 +/- 2.5 nM; Bmax = 52.0 +/- 14.0, 31.07 +/- 8.00 fmol/mg control and Alzheimer's disease values, respectively) cortices.(ABSTRACT TRUNCATED AT 250 WORDS)
O'Neill
C
C
Alzheimer's Disease Research Centre, Karolinska Institute, Department of Geriatric Medicine, Huddinge, Sweden.
Fowler
C J
CJ
Wiehager
B
B
Cowburn
R F
RF
Alafuzoff
I
I
Winblad
B
B
D000368:Aged; D000544:Alzheimer Disease / Q000378:metabolism*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D002712:Chlorides; D003000:Clonidine / Q000378:metabolism; D005260:Female; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006150:Guanine Nucleotides / Q000378:metabolism; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D008345:Manganese / Q000494:pharmacology; D017895:Manganese Compounds; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013570:Synaptic Membranes / Q000187:drug effects / Q000378:metabolism
D002712:Chlorides; D006150:Guanine Nucleotides; D017895:Manganese Compounds; D011942:Receptors, Adrenergic, alpha; D006165:Guanylyl Imidodiphosphate; D008345:Manganese; D019204:GTP-Binding Proteins; D003000:Clonidine; C025340:manganese chloride