Age related decline in aluminum-activated human platelet adenylate cyclase: post-receptor changes in cyclic AMP second messenger signal amplification in normal aging and dementia of the Alzheimer type.
Low, micromolar concentrations of aluminum (in the presence of NaF) were shown to strongly activate human platelet adenylate cyclase and provided a useful probe for evaluating cyclic AMP second messenger function distal to the receptor: The effect of normal aging and disease state on second messenger activity in man was studied by measurements of the aluminum-activated enzyme. A significant decline in aluminum-stimulated platelet adenylate cyclase activity in older, healthy subjects was observed. An age-associated decline in NaF-stimulated cyclic AMP synthesis was also demonstrated for normal, non-demented subjects. These findings suggest an age-associated lesion at the level of the guanine nucleotide regulatory protein/catalytic subunit of the adenylate cyclase complex. However, for patients with Alzheimer's disease no such decline in platelet adenylate cyclase activity was detected, and increased sensitivity to both aluminum and NaF was demonstrated.
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000375:Aging; D000535:Aluminum / Q000494:pharmacology*; D000544:Alzheimer Disease / Q000201:enzymology*; D001792:Blood Platelets / Q000201:enzymology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged
D000535:Aluminum; D000262:Adenylyl Cyclases