Adenosine receptors

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Thank you for visiting nature. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser or turn off compatibility mode in Internet Explorer. In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript. Adenosine is a key endogenous molecule that is released from cells and regulates tissue function via activating four G-protein-coupled adenosine receptors: A 1 , A 2A , A 2B and A 3. These receptors are abundantly expressed on the surface of immune cells as well as on endothelial, smooth muscle, epithelial cells, fibroblasts and cardiomyocytes.

Adenosine receptors

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. After an introduction on adenosine receptor subtypes, transduction mechanisms, and adenosine receptor regulation, this review will focus on the strueture of adenosine receptor ligands, and on the structural information contained in the deduced amino acid sequences of the recently cloned adenosine receptor cDNAs. Many tools for the delineation of receptor physiology and pharmacology, as well as some potential therapeutic agents, have become available in recent years. The structure—activity relationships SARs of these compounds will be discussed, with some emphasis on the insights that have been gained using molecular modeling techniques. In addition, information about the structure of the receptor gathered with the aid of receptor labeling agents will be discussed, and a detailed analysis of functional and structural domains of the receptor deduced from the amino acid sequences will be presented. The physiology, pharmacology, and therapeutic potential of adenosine receptors have been the subject of a number of recent reviews 3 , 6 — 8 and will not be discussed in any detail in the present article. The most extensively studied effector system coupled to adenosine receptors is the adenylate cyclase system. The adenosine receptors regulate the adenylate cyclase indirectly by activating guanine nucleotide regulatory proteins G proteins. It is clear, however, that the activation of G proteins by receptors is dependent on the presence of GTP and leads to the activation or inhibition of the effector system such as adenylate cyclase or phospholipases. It is now known that there are multiple regulatory steps in the process of receptor-G protein coupling and activation. This effect of sodium is now thought to be derived from a specific sodium—aspartate interaction in the second transmembrane domain of the receptor.

Figure 5: Adenosine receptor antagonists. Gerlach E, Becker BF, editors. Melani A.

Nucleoside transporters. The adenosine receptors or P1 receptors [1] are a class of purinergic G protein-coupled receptors with adenosine as the endogenous ligand. The adenosine receptors are commonly known for their antagonists caffeine , theobromine , and theophylline , whose action on the receptors produces the stimulating effects of coffee , tea and chocolate. Each type of adenosine receptor has different functions, although with some overlap. Most older compounds acting on adenosine receptors are nonselective, with the endogenous agonist adenosine being used in hospitals as treatment for severe tachycardia rapid heart beat , [9] and acting directly to slow the heart through action on all four adenosine receptors in heart tissue, [10] as well as producing a sedative effect through action on A 1 and A 2A receptors in the brain.

Adenosine is a ubiquitous endogenous autacoid whose effects are triggered through the enrollment of four G protein-coupled receptors: A 1 , A 2A , A 2B , and A 3. Due to the rapid generation of adenosine from cellular metabolism, and the widespread distribution of its receptor subtypes in almost all organs and tissues, this nucleoside induces a multitude of physiopathological effects, regulating central nervous, cardiovascular, peripheral, and immune systems. It is becoming clear that the expression patterns of adenosine receptors vary among cell types, lending weight to the idea that they may be both markers of pathologies and useful targets for novel drugs. This review offers an overview of current knowledge on adenosine receptors, including their characteristic structural features, molecular interactions and cellular functions, as well as their essential roles in pain, cancer, and neurodegenerative, inflammatory, and autoimmune diseases. Finally, we highlight the latest findings on molecules capable of targeting adenosine receptors and report which stage of drug development they have reached. Abstract Adenosine is a ubiquitous endogenous autacoid whose effects are triggered through the enrollment of four G protein-coupled receptors: A 1 , A 2A , A 2B , and A 3. Publication types Review.

Adenosine receptors

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. After an introduction on adenosine receptor subtypes, transduction mechanisms, and adenosine receptor regulation, this review will focus on the strueture of adenosine receptor ligands, and on the structural information contained in the deduced amino acid sequences of the recently cloned adenosine receptor cDNAs. Many tools for the delineation of receptor physiology and pharmacology, as well as some potential therapeutic agents, have become available in recent years. The structure—activity relationships SARs of these compounds will be discussed, with some emphasis on the insights that have been gained using molecular modeling techniques. In addition, information about the structure of the receptor gathered with the aid of receptor labeling agents will be discussed, and a detailed analysis of functional and structural domains of the receptor deduced from the amino acid sequences will be presented.

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Yasui, K. Adenosine modulates vascular endothelial growth factor expression via hypoxia-inducible factor-1 in human glioblastoma cells. Adenosine receptor-dopamine receptor interactions in the basal ganglia and their relevance for brain function. You are using a browser version with limited support for CSS. Moser, G. Association of stimulant use with dopaminergic alterations in users of cocaine, amphetamine, or methamphetamine: a systematic review and meta-analysis. Neuroprotection by adenosine in the brain: from A 1 receptor activation to A 2A receptor blockade. Victor-Vega, C. Tebano, M. Malek R. JAMA , — The potential therapeutic advantage of such an approach is that effects will be limited to sites where adenosine levels are elevated, i.

Adenosine, beside its role in the intermediate metabolism, mediates its physiological functions by interacting with four receptor subtypes named A 1 , A 2A , A 2B and A 3. All these receptors belong to the superfamily of G protein-coupled receptors that represent the most widely targeted pharmacological protein class. Since adenosine receptors are widespread throughout the body, they are involved in a variety of physiological processes and pathology including neurological, cardiovascular, inflammatory diseases and cancer.

The effect of cocaine exposure in fetal brains and the modulation of DA and adenosine effects have also been addressed; specifically, from E8 to E14 embryonic days, cocaine treatment induced changes in DA and adenosine signaling which increased basal cAMP levels in the striatum and cerebral cortex. Inhibition of the transcription hypoxia-inducible factor HIF-1 has been reported in astrocytes with neuromodulatory effects through MAPK and Akt modulation Gessi et al. The A 1 , together with A 2A receptors of endogenous adenosine play a role in regulating myocardial oxygen consumption and coronary blood flow. His research interests include the development of new computational tools fortire evaluation, analysis, and comparison of new DNA and protein sequence data. Provided by the Springer Nature SharedIt content-sharing initiative. Sleep regulation in adenosine A2A receptor-deficient mice. In addition, knockdown of A 2B AR by siRNA inhibited the release of pro-angiogenic growth factor, interleukin-8, in A human melanoma cells treated with chemotherapeutic agents like etoposide and doxorubicin [ ]. Evidence for a G-protein-coupled receptor kinase-mediated mechanism. In this section, we will describe the current state of knowledge about how adenosine signaling can interfere with common addictive psychostimulant consumption, focusing on data obtained from animal, particularly murine, models and from human studies. Hypoxia-induced desensitization and internalization of adenosine A1 receptors in the rat hippocampus.