Adenosine A2A receptor antagonism increases striatal glutamate outflow in dopamine-denervated rats.
The objective of the work was to study, by in vivo microdialysis, the effect of the adenosine A(2A) receptor antagonist 7-(2-phenylethyl)-5-amino-2-(2-furyl)-pyrazolo-[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine (SCH 58261) on glutamate outflow in the striata of unilateral 6-hydroxydopamine-infused rats. Two vertical microdialysis probes were implanted bilaterally in both the denervated striatum and in the intact striatum. Glutamate concentrations in the dialysate were determined by high-performance liquid chromatography (HPLC). Infusion of the adenosine A(2A) receptor antagonist SCH 58261 (50 nM), through the microdialysis fiber, significantly increased glutamate outflow from the denervated striatum while it decreased glutamate outflow from the intact striatum. The opposite effects of SCH 58261 on glutamate outflow in the intact and 6-hydroxydopamine-lesioned striatum might be attributed to blockade of striatal adenosine A(2A) receptors located on either striatal indirect output pathways or glutamatergic terminals. These results may be relevant to our understanding of the mechanism of action of adenosine A(2A) receptor antagonists in Parkinson's disease.
Corsi
Claudia
C
Department of Preclinical and Clinical Pharmacology, University of Florence, Viale Pieraccini 6, 50139, Florence, Italy.
Pinna
Annalisa
A
Gianfriddo
Marco
M
Melani
Alessia
A
Morelli
Micaela
M
Pedata
Felicita
F
D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D003714:Denervation; D004298:Dopamine / Q000502:physiology; D018698:Glutamic Acid / Q000378:metabolism*; D008297:Male; D017551:Microdialysis; D016627:Oxidopamine / Q000494:pharmacology; D058915:Purinergic P1 Receptor Antagonists; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D043705:Receptor, Adenosine A2A; D018047:Receptors, Purinergic P1 / Q000502:physiology; D013997:Time Factors; D014230:Triazoles / Q000494:pharmacology*
C098657:5-amino-7-(2-phenylethyl)-2-(2-furyl)pyrazolo(4,3-e)-1,2,4-triazolo(1,5-c)pyrimidine; D058915:Purinergic P1 Receptor Antagonists; D011743:Pyrimidines; D043705:Receptor, Adenosine A2A; D018047:Receptors, Purinergic P1; D014230:Triazoles; D018698:Glutamic Acid; D016627:Oxidopamine; D004298:Dopamine