Adenosine, glutamate and pH: interactions and implications

Abstract

Adenosine's role in the nervous system is multifaceted. As the core molecule of adenosine triphosphate (ATP), adenosine exists in equilibrium with the adenine nucleotide pool and contributes to cellular energy charge, a quantification of relative amounts of available ATP, ADP, AMP and adenosine. Beyond participating in overall energy balance and thus in maintaining cellular homeostasis, adenosine critically influences dynamic signaling in the nervous system. In particular, adenosine has an effect on and is affected by excitatory synaptic transmission. This report describes the ubiquitous nature of adenosine's influence, outlines specific scenarios of clinical import and highlights emerging knowledge about the regulation of adenosine.

A Drosophila adenosine receptor activates cAMP and calcium signaling

“…3). All these connections suggest that the proposed role for adenosine as a local paracrine and autocrine homeostatic regulator (Masino and Dulla, 2005;Newby, 1984;Cunha, 2001) could apply to both mammals and Drosophila. The adenosine pathways in Drosophila and mammals may therefore represent evolutionarily well-conserved homeostatic mechanisms.…”

“…Adenosine is an endogenous nucleoside that modulates numerous physiological processes, including oxygen and metabolic balance in tissues (Berne, 1963;Costa and Biaggioni, 1998), immune responses (Sitkovsky and Lukashev, 2005) and signaling in the nervous system (Masino and Dulla, 2005;Fredholm et al, 2005). Most of these roles in mammals are mediated by interaction of adenosine with specific G protein-coupled receptors (GPCRs).…”

Toward sophisticated basal ganglia neuromodulation: Review on basal ganglia deep brain stimulation

“…In the central nervous system, ADO regulates cerebral blood flow by signalling at A2A receptors, and to a lesser extent at A2B receptors (Cechova and Venton, 2008). As it is a product of ATP degradation, its release from cells is a sign of a high metabolic rate (Masino and Dulla, 2005). Thus, increases in extracellular ADO appear to match elevations in cerebral blood flow that result from increases in neural activity, directly amenable to measurement with fMRI (Phillips, 2004; Brundege and Dunwiddie, 1997).…”

Comparative Computational and Experimental Detection of Adenosine Using Ultrasensitive Surface-Enhanced Raman Spectroscopy

“…In addition to its major role in cardiac physiology, diagnosis, and therapy, adenosine also has important roles in the physiology of learning, memory, and sleep [ 9 , 10 , 11 ]; in the pathophysiology of brain disorders such as Parkinson’s disease, drug addiction, and depression [ 12 , 13 , 14 , 15 , 16 ]; and in the regulation of anti-secretory effect in the stomach, of anti-epileptic effect, and of renal functions [ 17 , 18 , 19 ]. Furthermore, because adenosine is a product of ATP degradation, its release from cells can also be correlated with a high metabolic rate or metabolic stress [ 20 ]. The extracellular concentration of adenosine in the brain has not only been linked to sleep regulation through slow wave activity [ 9 ], but has also been shown to modulate it [ 10 , 11 ].…”