Decreased beta-adrenoceptor-stimulated adenylyl cyclase activity in lymphocytes from Alzheimer's disease patients.
Previous studies have shown that in Alzheimer's disease post-mortem brain there are disruptions of both beta1-adrenoceptor-G-protein coupling and G-protein stimulation of adenylyl cyclase activity. Decreased beta-adrenoceptor stimulated adenylyl cyclase activity has also been shown in Alzheimer's disease primary skin fibroblasts. In the present study, we determined the regulation of adenylyl cyclase in Alzheimer's disease patients using an easily accessible tissue source, namely peripheral blood lymphocytes. beta-Adrenoceptor- and forskolin-stimulated adenylyl cyclase activities were investigated in lymphocytes from 12 Alzheimer's disease and 12 carefully matched and selected control subjects. No significant differences were found in basal or forskolin-stimulated enzyme activities between Alzheimer's disease and control lymphocytes. In contrast, isoprenaline-stimulated adenylyl cyclase activities were significantly lower in the Alzheimer's disease groups, as compared to controls. These results indicate that there is a widespread disruption of beta-adrenoceptor-G-protein-enzyme coupling in different tissues from Alzheimer's disease patients, and that adenylyl cyclase disturbances previously reported in Alzheimer's disease brain do not occur as a consequence of disease pathology or of terminal illness.
Garlind
A
A
Karolinska Institute, Department of Clinical Neuroscience and Family Medicine, Huddinge University Hospital, Sweden.
Johnston
J A
JA
Algotsson
A
A
Winblad
B
B
Cowburn
R F
RF
D000262:Adenylyl Cyclases / Q000187:drug effects*; D000368:Aged; D000544:Alzheimer Disease / Q000201:enzymology*; D005576:Colforsin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D008214:Lymphocytes / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism*
D011943:Receptors, Adrenergic, beta; D005576:Colforsin; D000262:Adenylyl Cyclases; D007545:Isoproterenol