ADENOSINE RECEPTORS IN RAT-BRAIN SYNAPTOSOMES - RECEPTOR CHARACTERIZATION AND RELATIONSHIPS WITH GLUTAMATE RELEASE

The role of adenosine receptor(s) activation in modulating glutamate release in synaptosomes isolated from different rat brain areas was investigated. Receptor binding studies with selective A1 and A2 adenosine receptor ligands were performed in parallel with functional studies on depolarization-induced increases of intrasynaptosomal calcium concentrations and glutamate release. Specific binding to the selective A1 ligand [H-3]-Cyclohexyladenosine was detected, with highest densities in hippocampal synaptosomes, followed by c. striatum and cortex. In contrast, no specific binding to the selective A2a ligand [H-3]CGS 21680 was demonstrable in synaptosomes from any of the studied brain areas, suggesting that no adenosine receptors belonging to this receptor subtype are present on rat brain pre-synaptic terminals. In parallel, the adenosine analogue cyclopentyladenosine (CPA) could partially inhibit the KCl-induced glutamate release from hippocampal synaptosomes. The agonist-induced effect was monophasic, dose-dependent, and already demonstrable at the 10(-8) M concentration, which indeed confirms that only A1 receptors inhibitory on calcium-dependent release are functionally present in synaptosomal preparations. The effect on glutamate release was likely due to the ability of CPA to partially counteract KCl-induced increases of intrasynaptosomal calcium concentrations. It is therefore concluded that rat hippocampal synaptosomes represent an adequate in vitro model to study the molecular and functional correlates of pre-synaptic adenosine receptors, and therefore investigate their role in both physiological and ischemia-associated pathological neurotransmission.