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Adenosine A 2A receptor antagonists prevent the increase in striatal glutamate levels induced by glutamate uptake inhibitors
Author(s) -
Pintor A.,
Galluzzo M.,
Grieco R.,
Pèzzola A.,
Reggio R.,
Popoli P.
Publication year - 2004
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.1471-4159.2003.02306.x
Subject(s) - glutamate receptor , adenosine , metabotropic glutamate receptor , pharmacology , microdialysis , metabotropic glutamate receptor 5 , extracellular , metabotropic glutamate receptor 6 , adenosine a1 receptor , biology , glutamic acid , chemistry , adenosine receptor , receptor , biochemistry , agonist , amino acid
Active uptake by neurons and glial cells is the main mechanism for maintaining extracellular glutamate at low, non‐toxic concentrations. Activation of adenosine A 2A receptors increases extracellular glutamate levels, while A 2A receptor antagonists reduce stimulated glutamate outflow. Whether a modulation of the glutamate uptake system is involved in the effects elicited by A 2A receptor blockers has never been investigated. This study examined the ability of adenosine A 2A receptor antagonists to prevent the increase in glutamate levels induced by blockade of the glutamate uptake. In rats implanted with a microdialysis probe in the dorsal striatum, perfusion with 4 m m l ‐ trans ‐pyrrolidine‐2,4‐dicarboxylic acid (PDC, a transportable competitive inhibitor of glutamate uptake), or 10 m m dihydrokainic acid (DHK, a non‐transportable competitive inhibitor that mainly blocks the glial glutamate transporter GLT‐1), significantly increased extracellular glutamate levels. The effects of PDC and DHK were completely prevented by the adenosine A 2A receptor antagonists SCH 58261 (0.01 mg/kg i.p.) and/or ZM 241385 (5 n m via probe). Since an impairment in glutamate transporter function is thought to play a major role in neurodegenerative disorders, the regulation of glutamate uptake may be one of the mechanisms of the neuroprotective effects of A 2A receptor antagonists.