A2A adenosine receptor overexpression and functionality, as well as TNF-alpha levels, correlate with motor symptoms in Parkinson's disease.
The antagonistic interaction between adenosine and dopamine receptors could have important pathophysiological and therapeutic implications in Parkinson's disease (PD). The primary aim of this study was to investigate the expression, affinity, and density of A(1), A(2A), A(2B), and A(3) adenosine receptors (ARs) and D(2) dopamine receptors (D(2)Rs) in PD. An increase in A(2A)AR density in putamen was found. The presence and functionality of ARs in human lymphocyte and neutrophil membranes from patients with PD revealed a specific A(2A)AR alteration compared with healthy subjects. A statistically significant linear correlation among the A(2A)AR density, functionality, or tumor necrosis factor-alpha (TNF-alpha) levels and Unified Parkinson's Disease Rating Scale (UPDRS) motor score was reported. Adenosine concentration and TNF-alpha levels were increased in plasma of patients with PD. In rat adrenal pheochromocytoma (PC12) cells, a widely useful model, adenosine antagonists decreased dopamine uptake, and an opposite effect was mediated by A(2A) agonists. This is the first report showing the presence of an A(2A)AR alteration in putamen in PD that mirrors a similar up-regulation in human peripheral blood cells. Moreover, the correlation found between A(2A)AR density or A(2A) agonist potency and UPDRS motor score highlights the central role of A(2A)ARs in the pharmacological treatment of PD.
Varani
Katia
K
Department of Clinical and Experimental Medicine, Pharmacology Section, University of Ferrara, via Fossato di Mortara 17-19 44100 Ferrara, Italy.
Vincenzi
Fabrizio
F
Tosi
Alice
A
Gessi
Stefania
S
Casetta
Ilaria
I
Granieri
Gino
G
Fazio
Patrik
P
Leung
Edward
E
MacLennan
Stephen
S
Granieri
Enrico
E
Borea
Pier Andrea
PA
D000241:Adenosine / Q000819:agonists / Q000037:antagonists & inhibitors / Q000097:blood; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001344:Autopsy; D000242:Cyclic AMP / Q000097:blood; D004298:Dopamine / Q000378:metabolism; D005260:Female; D006801:Humans; D008214:Lymphocytes / Q000737:chemistry; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000737:chemistry; D016716:PC12 Cells; D010300:Parkinson Disease / Q000097:blood / Q000235:genetics / Q000503:physiopathology*; D011699:Putamen / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D043705:Receptor, Adenosine A2A / Q000235:genetics*; D043704:Receptor, Adenosine A2B / Q000235:genetics; D043684:Receptor, Adenosine A3 / Q000235:genetics; D017448:Receptors, Dopamine D2 / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000235:genetics*
D012333:RNA, Messenger; D043705:Receptor, Adenosine A2A; D043704:Receptor, Adenosine A2B; D043684:Receptor, Adenosine A3; D017448:Receptors, Dopamine D2; D014409:Tumor Necrosis Factor-alpha; D000242:Cyclic AMP; D000241:Adenosine; D004298:Dopamine