Excitatory Transmitter Amino Acid Release from the Ischemic Rat Cerebral Cortex: Effects of Adenosine Receptor Agonists and Antagonists

Abstract

The effects of selective adenosine receptor agonists [N6-cyclopentyladenosine (CPA) and N-ethylcarboxamidoadenosine (NECA)] and antagonists [8-cyclopentyl-1,3-dipropylxanthine (DPCPX) and 9-chloro-2-(2-furanyl)-5,6-dihydro-1,2,4-triazolo[1,5-c]quinazoline-5-im ine (CGS-15943A)] on aspartate and glutamate release from the ischemic rat cerebral cortex were studied with the cortical cup technique. Cerebral ischemia (for 20 min) was elicited by four-vessel occlusion. Excitatory amino acid releases were compared from control ischemic rats and drug-treated rats. Basal levels of aspartate and glutamate release were not greatly affected by pretreatment with the adenosine receptor agonists or antagonists. However, CPA (10(-10) M) and NECA (10(-9) M) significantly inhibited the ischemia-evoked release of aspartate and glutamate into cortical superfusates. The ability to block ischemia-evoked release of excitatory amino acids was not evident at higher concentrations of CPA (10(-6) M) or NECA (10(-5) M). The selective A1 receptor antagonist DPCPX also had no effect on release when administered at a low dosage (0.01 mg/kg, i.p.) but blocked the ischemia-evoked release of aspartate and glutamate at a higher dosage (0.1 mg/kg). Evoked release was inhibited by the selective A2 receptor antagonist CGS-15943A (0.1 mg/kg, i.p.). Thus, adenosine and its analogs may suppress ischemia-evoked release of excitatory neurotransmitter amino acids via high-affinity A1 receptors, whereas coactivation of lower-affinity A2 receptors may block (or reverse) the A1-mediated response.

Anxiolytic activity of adenosine receptor activation in mice

“…This might suggest that activation of A2 receptors is able to suppress the effects of activating Al receptors. A similar inhibition by A2 (Simpson et al, 1992). It has also been invoked to explain the interactions of adenosine receptor agonists on catalepsy observed by Zarrindast et al (1993).…”

Further characterization of [3H]‐CGS 21680 binding sites in the rat striatum and cortex

“…It has already been shown that the mRNA encoding this receptor is transiently expressed in the developing cortex (Weaver, 1993) and that A2A receptor activation can regulate the release of GABA and glutamate from the ischaemic cortex Simpson et al, 1992). In addition the A2A receptor regulates neuronal excitability (Sebastiao et al, 1994) and acetylcholine release in the hippocampus (Cunha et al, 1994b).…”

Input-Specific Modulation of Neurotransmitter Release in the Lateral Horn of the Spinal Cord via Adenosine Receptors

“…Under these conditions, the concentration of adenosine available increases and activates A1Rs to reduce excitotoxicity (Fowler, 1989;Simpson et al, 1992;Katchman and Hershkowitz, 1993;Sweeney, 1997). A2 A Rs are often considered excitatory, potentiating the release of excitatory neurotransmitters .…”