Premium
Adenosine A 2A receptors control the extracellular levels of adenosine through modulation of nucleoside transporters activity in the rat hippocampus
Author(s) -
PintoDuarte António,
Coelho Joana E.,
Cunha Rodrigo A.,
Ribeiro Joaquim Alexandre,
Sebastião Ana M.
Publication year - 2005
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2005.03071.x
Subject(s) - adenosine , adenosine a1 receptor , adenosine a3 receptor , adenosine receptor , purinergic signalling , cgs 21680 , stimulation , chemistry , agonist , adenosine a2b receptor , medicine , receptor , endocrinology , nucleoside , pharmacology , biology , biochemistry
Adenosine, a neuromodulator of the CNS, activates inhibitory‐A 1 receptors and facilitatory‐A 2A receptors; its synaptic levels are controlled by the activity of bi‐directional equilibrative nucleoside transporters. To study the relationship between the extracellular formation/inactivation of adenosine and the activation of adenosine receptors, we investigated how A 1 and A 2A receptor activation modifies adenosine transport in hippocampal synaptosomes. The A 2A receptor agonist, CGS 21680 (30 n m ), facilitated adenosine uptake through a PKC‐dependent mechanism, but A 1 receptor activation had no effect. CGS 21680 (30 n m ) also increased depolarization‐induced release of adenosine. Both effects were prevented by A 2A receptor blockade. A 2A receptor‐mediated enhancement of adenosine transport system is important for formatting adenosine neuromodulation according to the stimulation frequency, as: (1) A 1 receptor antagonist, DPCPX (250 n m ), facilitated the evoked release of [ 3 H]acetylcholine under low‐frequency stimulation (2 Hz) from CA3 hippocampal slices, but had no effect under high‐frequency stimulation (50 Hz); (2) either nucleoside transporter or A 2A receptor blockade revealed the facilitatory effect of DPCPX (250 n m ) on [ 3 H]acetylcholine evoked‐release triggered by high‐frequency stimulation. These results indicate that A 2A receptor activation facilitates the activity of nucleoside transporters, which have a preponderant role in modulating the extracellular adenosine levels available to activate A 1 receptors.