Adenosine receptors

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Federal government websites often end in. The site is secure. Adenosine is a neuromodulator that plays a pivotal role in maintaining adequate oxygen and energy supply throughout the body, 1 The actions of adenosine are mediated through specific cell-surface receptors, of which at least two subtypes are known, A 1 and A 2. Due to its potent actions on many organs and systems, adenosine is an obvious target for the development of new drugs, 2 and in the past decade adenosine receptors have become a subject of intense investigation. Potential therapeutic applications for agonists include, for instance, the prevention of reperfusion injury after cardiac ischemia or stroke, and the treatment of hypertension and epilepsy.

Adenosine receptors

Adenosine receptors AR are a family of G-protein coupled receptors, comprised of four members, named A 1 , A 2A , A 2B , and A 3 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 , adenosine acts as a neuromodulator, exerting different functions depending on the type of AR and consequent cellular signaling involved. In the CNS, A 1 receptors are widely distributed in the cortex, hippocampus, and cerebellum, A 2A receptors are localized mainly in the striatum and olfactory bulb, while A 2B and A 3 receptors are found at low levels of expression. In addition, AR are able to form heteromers, both among themselves e. Nowadays, we know that adenosine, by acting on adenosine A 1 and A 2A receptors, is known to antagonistically modulate dopaminergic neurotransmission and therefore reward systems, being A 1 receptors colocalized in heteromeric complexes with D 1 receptors, and A 2A receptors with D 2 receptors. This review documents the present state of knowledge of the contribution of AR, particularly A 1 and A 2A , to psychostimulants-mediated effects, including locomotor activity, discrimination, seeking and reward, and discuss their therapeutic relevance to psychostimulant addiction. Studies presented in this review reinforce the potential of A 1 agonists as an effective strategy to counteract psychostimulant-induced effects. The overall analysis of presented data provide evidence that excitatory modulation of A 1 and A 2A receptors constitute promising tools to counteract psychostimulants addiction. Drug addiction is a complex chronic cognitive disorder characterized by drug seeking and compulsive use, which is difficult to control despite its harmful consequences. According to DSM-5 American Psychiatric Association, , which is used to define mental disorders in epidemiologic studies, it is now accepted that the criteria used to clinically define the terms abuse and dependence should be combined to form a new category known as Substance use disorders , including craving as a new criterion to increase diagnostic accuracy Hasin et al. In terms of epidemiology, drug addiction is currently a global health problem, as can be deduced from comparison of data obtained from the Global Burden of Diseases Study between and

Bailey, A.

Federal government websites often end in. The site is secure. To date, four AR subtypes have been cloned and identified in different tissues. These receptors have distinct localization, signal transduction pathways and different means of regulation upon exposure to agonists. This review will describe the biochemical characteristics and signaling cascade associated with each receptor and provide insight into how these receptors are regulated in response to agonists. Recent observations of oligomerization of these receptors into homo- and heterodimers will be discussed. In addition, the importance of these receptors in the regulation of normal and pathological processes such as sleep, the development of cancers and in protection against hearing loss will be examined.

Federal government websites often end in. The site is secure. Whereas the A2AR has been implicated in normal aging and enhancing neurotoxicity in multiple neurodegenerative diseases, the inhibitory A1R has traditionally been ascribed to have a neuroprotective function in various brain insults. This review provides a summary of the emerging role of prolonged A1R signaling and its potential cross-talk with A2AR in the cellular basis for increased neurotoxicity in neurodegenerative disorders. Adenosine signaling has been well studied in the brain and plays a complex role in multiple physiological and pathophysiological processes. Through a family of four G protein-coupled adenosine receptors, A1, A2A, A2B, and A3 [ 1 ], adenosine exerts neuromodulatory effects throughout the brain, affecting crucial processes such as normal neuronal signaling [ 2 , 3 ], astrocytic function [ 4 , 5 , 6 ], learning and memory [ 7 , 8 , 9 , 10 ], motor function [ 11 ], feeding [ 12 ], control of sleep [ 13 ], and normal aging processes [ 9 , 14 , 15 ].

Adenosine receptors

Federal government websites often end in. The site is secure. To date, four AR subtypes have been cloned and identified in different tissues. These receptors have distinct localization, signal transduction pathways and different means of regulation upon exposure to agonists. This review will describe the biochemical characteristics and signaling cascade associated with each receptor and provide insight into how these receptors are regulated in response to agonists. Recent observations of oligomerization of these receptors into homo- and heterodimers will be discussed. In addition, the importance of these receptors in the regulation of normal and pathological processes such as sleep, the development of cancers and in protection against hearing loss will be examined.

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Preti, D. Sign up for Nature Briefing. Similar methods have been used to explore the C8-region of xanthine antagonists. Blood Flow Metab. Adenosine A2A agonist reduces paralysis after spinal cord ischemia: correlation with A2A receptor expression on motor neurons. Adenosine regulates via two different types of receptors, the accumulation of cyclic AMP in cultured brain cells. Absence of the adenosine A2A receptor or its chronic blockade decrease ethanol withdrawal-induced seizures in mice. The mechanisms underlying rapid desensitization often involve receptor phosphorylation by a family of G protein-coupled receptor kinases GRKs resulting in their preferential binding to arrestins molecules. Sebastiao A. Brackett, L. Immunomodulatory impact of the A2A adenosine receptor on the profile of chemokines produced by neutrophils.

Adenosine is a naturally occurring nucleoside that is distributed ubiquitously throughout the body as a metabolic intermediary. In the brain, adenosine functions as an important upstream neuromodulator of a broad spectrum of neurotransmitters, receptors, and signaling pathways.

Liver Physiol. In mouse brain, however, adenosine agonists inhibit histamine-induced phosphoinositide turnover. Partially adenosine deaminase-deficient mice develop pulmonary fibrosis in association with adenosine elevations. Aden, U. His research interests include the development of new computational tools fortire evaluation, analysis, and comparison of new DNA and protein sequence data. The physiological activity of adenine compounds with especial reference to their action upon the mammalian heart. Retey J. Search Search articles by subject, keyword or author. The ratiom;le behind this limitation is that those residues that are conserved throughout a family, and certainly between closely related receptors like both adenosine receptor subtypes, are likely to serve similar functions. Long-term activation of adenosine A 2a receptors blocks glutamate excitotoxicity in cultures of avian retinal neurons.