Up-regulation of adenosine receptors in the frontal cortex in Alzheimer's disease.
Adenosine receptors are G-protein coupled receptors which modulate neurotransmitter release, mainly glutamate. Adenosine A(1) and A(2A) receptors were studied in post-mortem human cortex in Alzheimer's disease (AD) and age-matched controls. Total adenosine A(1) receptor number, determined by radioligand binding assay, using [(3)H]DPCPX, was significantly increased in AD cases in early and advanced stages without differences with the progression of the disease. A significant increase of A(1)R (37 kDa) levels was also observed by Western blot in early and advanced stages of AD. In addition, increased numbers of adenosine A(2A) receptors were observed in AD samples as determined by a binding assay using [(3)H]ZM 241385 as a radioligand and by Western blot. Increased binding and protein expression levels of adenosine receptors were not associated with increased mRNA levels coding A(1) and A(2A) receptors. Finally, increased A(1) and A(2A) receptor-mediated response was observed. These results show up-regulation of adenosine A(1) and A(2A) receptors in frontal cortex in AD, associated with sensitization of the corresponding transduction pathways.
Albasanz
José L
JL
Departamento de Química Inorgánica, Orgánica y Bioquímica, Facultad de Químicas, Centro Regional de Investigaciones Biomédicas, Universidad de Castilla-La Mancha, Ciudad Real, Spain.
Perez
Sandra
S
Barrachina
Marta
M
Ferrer
Isidro
I
Martín
Mairena
M
D000262:Adenylyl Cyclases / Q000378:metabolism; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology*; D000704:Analysis of Variance; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D005260:Female; D005625:Frontal Lobe / Q000378:metabolism*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D006801:Humans; D008297:Male; D008875:Middle Aged; D011485:Protein Binding / Q000187:drug effects; D018047:Receptors, Purinergic P1 / Q000235:genetics / Q000378:metabolism*; D014227:Triazines / Q000378:metabolism; D014230:Triazoles / Q000378:metabolism; D014316:Tritium / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology*; D014970:Xanthines / Q000378:metabolism
D018047:Receptors, Purinergic P1; D014227:Triazines; D014230:Triazoles; D014970:Xanthines; C097270:ZM 241385; D014316:Tritium; D005576:Colforsin; D016244:Guanosine 5'-O-(3-Thiotriphosphate); C051360:1,3-dipropyl-8-cyclopentylxanthine; D000242:Cyclic AMP; D000262:Adenylyl Cyclases