Neuromodulatory roles of purines

Abstract

AbstractIn the present overview we focus on two aspects: (a) the role of adenosine as an endogenous cerebroprotective agent and (b) the possible significance of adenosine‐dopamine interactions. Adenosine is a normal constituent of the brain extracellular environment. Its levels greatly increase upon neuronal excitation or as a consequence of decreased supply of metabolic substrates. Via its receptors it tends to limit its own formation in several ways. By increasing blood flow and glucose uptake it increases substrate supply. By decreasing the release of excitatory neurotransmitters and by causing hyperpolarization it decreases energy demand. This suggests a role as an endogenous cerebroprotective agent, something which is supported by several lines of pharmacological evidence.The adenosine A2a receptor is enriched in dopamine rich‐areas of the brain and it has been found to be colocalized with dopamine D2 receptors on medium‐sized spiny neurons in the striatum. Recent evidence shows that A2 agonists decrease agonist binding to dopamine D2 receptors. Furthermore, adenosine receptor antagonists have been shown to produce behavioural effects that are due to enhanced dopaminergic neurotransmission. It is suggested that the A2‐ D2‐receptor interactions may explain some of the stimulatory effects of low doses of caffeine. © 1993 Wiley‐Liss, Inc.