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 A1, A2A, A2B, and A3 adenosine receptors (ARs) and D2 dopamine receptors (D2Rs) in PD. An increase in A2AAR density in putamen was found. The presence and functionality of ARs in human lymphocyte and neutrophil membranes from patients with PD revealed a specific A2AAR alteration compared with healthy subjects. A statistically significant linear correlation among the A2AAR density, functionality, or tumor necrosis factor- (TNF-) levels and Unified Parkinson’s Disease Rating Scale (UPDRS) motor score was reported. Adenosine concentration and TNF- 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 A2A agonists. This is the first report showing the presence of an A2AAR alteration in putamen in PD that mirrors a similar up-regulation in human peripheral blood cells. Moreover, the correlation found between A2AAR density or A2A agonist potency and UPDRS motor score highlights the central role of A2AARs in the pharmacological treatment of PD.—Varani, K., Vincenzi, F., Tosi, A., Gessi, S., Casetta, I., Granieri, G., Fazio, P., Leung, E., MacLennan, S., Granieri, E., Borea, P. A. A2A adenosine receptor overexpression and functionality, as well as TNF- levels, correlate with motor symptoms in Parkinson’s disease.
A2A adenosine receptor overexpression and functionality, as well as TNF-alpha levels, correlate with motor symptoms in Parkinson's disease.
VARANI, Katia;VINCENZI, Fabrizio;TOSI, ALICE;GESSI, Stefania;CASETTA, Ilaria;GRANIERI, Gino;FAZIO, Patrik;GRANIERI, Enrico Gavino Giuseppe;BOREA, Pier Andrea
2010
Abstract
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 A1, A2A, A2B, and A3 adenosine receptors (ARs) and D2 dopamine receptors (D2Rs) in PD. An increase in A2AAR density in putamen was found. The presence and functionality of ARs in human lymphocyte and neutrophil membranes from patients with PD revealed a specific A2AAR alteration compared with healthy subjects. A statistically significant linear correlation among the A2AAR density, functionality, or tumor necrosis factor- (TNF-) levels and Unified Parkinson’s Disease Rating Scale (UPDRS) motor score was reported. Adenosine concentration and TNF- 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 A2A agonists. This is the first report showing the presence of an A2AAR alteration in putamen in PD that mirrors a similar up-regulation in human peripheral blood cells. Moreover, the correlation found between A2AAR density or A2A agonist potency and UPDRS motor score highlights the central role of A2AARs in the pharmacological treatment of PD.—Varani, K., Vincenzi, F., Tosi, A., Gessi, S., Casetta, I., Granieri, G., Fazio, P., Leung, E., MacLennan, S., Granieri, E., Borea, P. A. A2A adenosine receptor overexpression and functionality, as well as TNF- levels, correlate with motor symptoms in Parkinson’s disease.I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
