ABSTRACT
The endogenous purine nucleoside adenosine (ADO) activates discrete extracellular receptors (termed P1 receptors) to serve as an inhibitory modulator of cellular and tissue function (1,2). ADO has been characterized as a ‘‘homeostatic’’ or ‘‘retaliatory’’ modulator of cellular activity (3). Tissue levels of extracellular ADO increase locally during periods of pathophysiological stress (e.g., tissue trauma and inflammation, ischemia, or seizures). Extracellular ADO accumulation may reflect the direct release of ADO itself or the release of ATP, which is degraded by extracellular nucleotidases to ADO (4) (Fig. 1). ADO in the extracellular space activates P1 receptors to elicit a variety of responses that tend to counteract the initial adverse stimulus, thereby restoring cellular function toward normal (5,6). ADO is rapidly inactivated in extracellular fluids (a half-life on the order of seconds) (7), and its endogenous actions are highly localized. Four subtypes of the P1 family of G-protein-coupled receptors have been identified and cloned: A1, A2A, A2B, and A3.
