Adenosine receptors (AR) are a family of G-protein coupled receptors, comprised of four members, named A1, A2A, A2B, and A3 receptors, found widely distributed in almost all human body tissues and organs. To date, they are known to participate in a large variety of physiopathological responses, which include vasodilation, pain, and inflammation. In particular, in the central nervous system (CNS...

Kitchen, Amy M., Tadeusz J. Scislo, and Donal S. O’Leary. NTS A2a purinoceptor activation elicits hindlimb vasodilation primarily via a b-adrenergic mechanism. Am J Physiol Heart Circ Physiol 278: H1775–H1782, 2000.— Previously, we have shown that activation of adenosine A2a receptors in the subpostremal nucleus tractus solitarii (NTS) via microinjection of the selective A2a receptor agonist CG...

The adenosine A2A receptor is a G-protein-coupled receptor (GPCR) that has been extensively studied during the past few decades because it offers numerous possibilities for therapeutic applications. Herein we describe adenosine A2A receptor distribution, signaling pathways, pharmacology, and molecular structure, followed by a summary and SAR discussion of the most relevant series of adenosine A...

Adenosine either inhibits or facilitates synaptic transmission through A1 or A2A receptors, respectively. Since A2A receptor density increases in the limbic cortex of aged (24 mo) compared with young adult rats (2 mo), we tested if A2A receptor modulation of synaptic transmission was also increased in aged rats. The A2A receptor agonist, CGS21680 (10 nM), caused a larger facilitation of the fie...

Adenosine A2A receptor antagonists provide a promising nondopaminergic approach to the treatment of Parkinson's disease (PD). Initial clinical trials of A2A antagonists targeted PD patients who had already developed treatment complications known as L-3,4-dihydroxyphenylalanine (L-DOPA)-induced dyskinesia (LID) in an effort to improve symptoms while reducing existing LID. The goal of this study ...

In previous studies, we have shown that the inactivation of the adenosine A2A receptor exacerbates chronic cerebral hypoperfusion-induced white matter lesions (WMLs) by enhancing neuroinflammatory responses. However, the molecular mechanism underlying the effect of the adenosine A2A receptor remains unknown. Recent studies have demonstrated that cystatin F, a potent endogenous cysteine protease...

Pharmacologic inactivation or genetic deletion of adenosine A2A receptors protects ischemic neurons in adult animals, but studies in neonatal hypoxia-ischemia (H-I) are inconclusive. The present study in neonatal piglets examined the hypothesis that A2A receptor signaling after reoxygenation from global H-I contributes to injury in highly vulnerable striatal neurons where A2A receptors are enri...

Typical antipsychotics, potent D2 dopamine receptor antagonists, are the most commonly used drugs in the treatment of bipolar disorders. In the central nervous system, the discovery of antagonistic interactions between A2A adenosine receptors and D2 dopamine receptors suggests that the adenosine system may be involved in the pathogenesis of different psychiatric disorders and in the therapeutic...

Okusa, Mark D. A2A adenosine receptor: a novel therapeutic target in renal disease. Am J Physiol Renal Physiol 282: F10–F18, 2002.— Present strategies in the treatment of inflammatory renal injury have focused on developing agents that specifically target individual mechanisms thought to contribute toward the pathogenesis of the disease. Such an approach is hindered by redundancies in the infla...

Background: The A2A-receptor engages Gs by restricted collision coupling and lacks a palmitoyl moiety in its C-terminus. Result: Engineering palmitoylated cysteine into the C-terminus relieved restricted collision coupling and resulted in accelerated diffusion of the agonist-liganded A2A-receptor. Conclusion: Restricted collision coupling arises from limits imposed on receptor diffusion. Signif...