Adenosine A2A receptors are up-regulated in Pick's disease frontal cortex

Adenosine A(2A) receptors (A(2A)R) are highly expressed in striatum. However, they are also present in extrastriatal structures. A(2A)R were studied in post-mortem human frontal cortex from Pick's disease (PiD) and age-matched non-demented controls by radioligand binding assays, Western-blotting, real-time PCR and adenylyl cyclase activity determination. Saturation binding assay using [H-3]ZM 241385, a selective A(2A) antagonist, as radioligand revealed a significant increase in total adenosine A(2A)R numbers (B-max) in frontal cortex from PiD samples (191% of control B-max), suggesting up-regulation of this receptor. A significant increase in the level of A(2A)R was also detected by Western-blotting. Furthermore, expression of mRNA coding A(2A)R determined by quantitative real-time PCR was enhanced. In agreement, stimulation of adenylyl cyclase by CGS 21680, a selective A(2A) receptor agonist, was significantly strengthened. Up-regulation of A(2B) receptors and their corresponding mRNA was also observed. These results show that A(2A) adenosine receptor/adenylyl cyclase transduction pathway is up-regulated and sensitized in frontal cortex brain from PiD.