Enhanced ATP release and CD73-mediated adenosine formation sustain adenosine A_2A receptor over-activation in a rat model of Parkinson's disease.

ABSTRACT:

Background and purpose

Parkinson's disease (PD) involves an initial loss of striatal dopamine terminals evolving into degeneration of dopamine neurons in substantia nigra (SN), which can be modelled by 6-hydroxydopamine (6-OHDA) administration. Adenosine A_2A receptor blockade attenuates PD features in animal models, but the source of the adenosine causing A_2A receptor over-activation is unknown. As ATP is a stress signal, we have tested if extracellular catabolism of adenine nucleotides into adenosine (through ecto-5'-nucleotidase or CD73) leads to A_2A receptor over-activation in PD.

Experimental approach

Effects of blocking CD73 with α,β-methylene ADP (AOPCP) were assayed in 6-OHDA-treated rats and dopamine-differentiated neuroblastoma SH-SY

SUBMITTER: Carmo M 

PROVIDER: S-EPMC6715785 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature