Adenosine A2a Receptor-Mediated Modulation of Striatal [3H]GABA and [3H]Acetylcholine Release
Article first published online: 28 JUN 2008
Journal of Neurochemistry
Volume 62, Issue 3, pages 960–966, March 1994
How to Cite
Kirk, I. P. and Richardson, P. J. (1994), Adenosine A2a Receptor-Mediated Modulation of Striatal [3H]GABA and [3H]Acetylcholine Release. Journal of Neurochemistry, 62: 960–966. doi: 10.1046/j.1471-4159.1994.62030960.x
- Issue published online: 28 JUN 2008
- Article first published online: 28 JUN 2008
- Recieved June 1, 1993; revised July 2 1993; accepted July 22, 1993.
Abstract: The ability of adenosine agonists to modulate K+-evoked 4D†-[3H]aminobutyric acid ([3H]GABA) and acetylcholine (ACh) release from rat striatal synaptosomes was investigated. The A2a receptor-selective agonist CGS 21680 inhibited Ca2+-dependent [3H]GABA release evoked by 15 mM KCI with a maximal inhibition of 29 ± 4% (IC50 of ∼4 ± 10 −12M). The relative order of potency of three agonists was CGS 21680 ± 5′-N-ethylcarboxamidoadenosine > R-phenylisopropyladenosine (R-PIA), with the inhibition being blocked by A2a receptor-selective antagonists (CP 66,713 and CGS 15943A) but not by the A1-selective antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX). When release of [3H]GABA was evoked by 30 mM KCI, no significant inhibition was observed. In contrast, CGS 21680 stimulated the release of [3H]ACh evoked by 30 mM KCI, with a maximal stimulation of 26 ± 5% (IC50 of ∼10−11M). This effect was blocked by CP 66,713 but not by DPCPX. The A1 agonist R-PIA inhibited [3H]ACh release, an effect blocked by DPCPX. It is concluded that adenosine A2a receptors are present on both GABAergic and cholinergic striatal nerve terminals where they inhibit and stimulate transmitter release, respectively. Key Words: GABA—Acetylcholine—Adenosine receptors—Striatum.