Adenosine A2A receptors are up-regulated in Pick's disease frontal cortex.
Adenosine A2A receptors (A2AR) are highly expressed in striatum. However, they are also present in extrastriatal structures. A2AR 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 [3H]ZM 241385, a selective A2A antagonist, as radioligand revealed a significant increase in total adenosine A2AR numbers (Bmax) in frontal cortex from PiD samples (191% of control Bmax), suggesting up-regulation of this receptor. A significant increase in the level of A2AR was also detected by Western-blotting. Furthermore, expression of mRNA coding A2AR determined by quantitative real-time PCR was enhanced. In agreement, stimulation of adenylyl cyclase by CGS 21680, a selective A2A receptor agonist, was significantly strengthened. Up-regulation of A2B receptors and their corresponding mRNA was also observed. These results show that A2A adenosine receptor/adenylyl cyclase transduction pathway is up-regulated and sensitized in frontal cortex brain from PiD.
Albasanz
José Luís
JL
Departamento de Química Inorgánica, Orgánica y Bioquímica, Facultad de Químicas, Centro Regional de Investigaciones Biomédicas, Universidad de Castilla-La Mancha, Ciudad Real, Spain.
Rodríguez
Agustín
A
Ferrer
Isidro
I
Martín
Mairena
M
D000262:Adenylyl Cyclases / Q000378:metabolism; D015153:Blotting, Western; D005625:Frontal Lobe / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D020774:Pick Disease of the Brain / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D043705:Receptor, Adenosine A2A / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
D012333:RNA, Messenger; D043705:Receptor, Adenosine A2A; D000262:Adenylyl Cyclases