Up-regulation of adenosine A1 receptors in frontal cortex from Pick's disease cases.
The adenosine A(1) receptor (A(1)R)-adenylyl cyclase (AC) pathway was studied in post-mortem human frontal and occipital cortex from Pick's disease (PiD) cases and age-matched nondemented controls. In frontal cortex, the main brain area affected in PiD, A(1)Rs, determined by radioligand binding, Western blotting and real-time PCR assays, were significantly increased in PiD samples, suggesting up-regulation of this receptor. AC activity was determined in basal and stimulated conditions via stimulatory guanine nucleotide binding proteins (Gs) using GTP, or directly with forskolin. Basal AC activity was reduced in brains from PiD cases. This agrees with the decrease in AC type I (AC I) level detected by Western blotting. However, inhibition of forskolin-stimulated AC activity by a selective A(1)R agonist was significantly increased in brains from PiD. In occipital cortex, adenosine A(1)R numbers were similar in control and PiD cases, and no significant differences were found in A(1)R-mediated AC inhibition. These results show that the adenosine A(1)R-AC transduction pathway is specifically up-regulated and sensitized in frontal cortex brain in PiD.
Departamento de Química Inorgánica, Orgánica y Bioquímica, Facultad de Químicas, Centro Regional de Investigaciones Biomédicas, Universidad de Castilla-La Mancha, Ciudad Real, Spain.
José Luis
JL
Albasanz
Agustín
A
Rodríguez
Isidro
I
Ferrer
Mairena
M
Martín
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D058907:Adenosine A1 Receptor Agonists; D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000378:metabolism; D000368:Aged; D001921:Brain / Q000201:enzymology; D002102:Cadaver; D002462:Cell Membrane / Q000378:metabolism; D005576:Colforsin / Q000494:pharmacology; D005260:Female; D005625:Frontal Lobe / Q000378:metabolism*; D006801:Humans; D008297:Male; D009778:Occipital Lobe / Q000378:metabolism; D020774:Pick Disease of the Brain / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D043682:Receptor, Adenosine A1 / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation; D014970:Xanthines / Q000378:metabolism
D058907:Adenosine A1 Receptor Agonists; D000067956:Adenylyl Cyclase Inhibitors; D012333:RNA, Messenger; D043682:Receptor, Adenosine A1; D014970:Xanthines; D005576:Colforsin; C027513:N(6)-cyclohexyladenosine; C051360:1,3-dipropyl-8-cyclopentylxanthine; D000262:Adenylyl Cyclases; D000241:Adenosine