Effects of adenosine A1 and A2A receptor activation on the evoked release of glutamate from rat cerebrocortical synaptosomes

• Published in: British journal of pharmacology Vol. 136; no. 3; pp. 434 - 440
• Main Authors: Marchi, Mario, Raiteri, Luca, Risso, Francesca, Vallarino, Annalisa, Bonfanti, Andrea, Monopoli, Angela, Ongini, Ennio, Raiteri, Maurizio
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.06.2002; Nature Publishing
• Subjects: A1 receptors; A2A receptors; Adenosine; Adenosine - analogs & derivatives; Adenosine - pharmacology; Adenosinic and purinergic receptors; Analysis of Variance; Animals; Biological and medical sciences; Cell receptors; Cell structures and functions; Central nervous system; Central neurotransmission. Neuromudulation. Pathways and receptors; cerebral cortex; Cerebral Cortex - metabolism; Cerebral Cortex - ultrastructure; Chromatography, High Pressure Liquid - methods; Fundamental and applied biological sciences. Psychology; glutamate release; Glutamic Acid - metabolism; In Vitro Techniques; ischaemia; Male; Molecular and cellular biology; Phenethylamines - pharmacology; Purinergic P1 Receptor Agonists; Pyrimidines - pharmacology; Rats; Rats, Sprague-Dawley; Receptor, Adenosine A2A; SCH58261; Synaptosomes - metabolism; Triazoles - pharmacology; Vertebrates: nervous system and sense organs; Xanthines - pharmacology; Cerebral cortex; Rat; Rodentia; Central nervous system; A1 Adenosine receptor; Glutamate; In vitro; A2A adenosine receptor; Vertebrata; Regulation(control); Synaptosome; Mammalia; Animal; Excitatory aminoacid; Release; Brain (vertebrata)
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1038/sj.bjp.0704712

The effects of adenosine A2A and A1 receptor activation on the release of glutamate were studied in rat cerebral cortex synaptosomes exposed in superfusion to adenosine receptor ligands. Adenosine (0.1 μM) produced a significant potentiation of the Ca2+‐dependent K+(15 mM)‐evoked [3H]‐D‐aspartate overflow (20.4±3.5%), which was blocked by A2A blocker SCH58261 (0.1 μM). At higher concentrations (10 – 1000 μM) adenosine inhibited in a DPCPX‐sensitive manner the Ca2+‐dependent K+‐evoked [3H]‐D‐aspartate overflow. The inhibitory effect of adenosine at 1000 μM was significantly increased by SCH58261. This inhibition was antagonized by 1 μM DPCPX. Adenosine did not produce any effect on basal release. The A2A receptor agonist CGS 21680 was ineffective on basal release, but stimulated the Ca2+‐dependent K+‐evoked overflow of [3H]‐D‐aspartate (EC50 ≃ 1 pM). The effect of 0.01 nM CGS 21680 was totally sensitive to the A2A receptor antagonist SCH58261 (IC50 ≃5 nM). The A1 receptor agonist CCPA inhibited the Ca2+‐dependent K+‐evoked [3H]‐D‐aspartate overflow (EC50 ≃ 20 nM). The effect of 100 nM CCPA was abolished by 100 nM of the A1 receptor antagonist DPCPX. The K+(15 mM)‐evoked overflow of endogenous glutamate was enhanced by CGS 21680 (0.01 nM) and inhibited by CCPA (0.1 μM). The effect of CGS 21680 was abolished by SCH58261 (0.1 μM) and that of CCPA by DPCPX (0.1 μM). It is concluded that adenosine and adenosine receptor agonists modulate glutamate release by activating inhibitory A1 and excitatory A2A receptors present on glutamatergic terminals of the rat cerebral cortex. British Journal of Pharmacology (2002) 136, 434–440; doi:10.1038/sj.bjp.0704712