Adenosine receptors

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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. Xanthine derivatives such as caffeine and theophylline act as non-selective antagonists at A 1 and A 2A receptors in both heart and brain and so have the opposite effect to adenosine, producing a stimulant effect and rapid heart rate.

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.

Pickens, C. Kelley, A. A 2A AR have a more restrictive localization in adenosine receptors striatum and olfactory bulb [ 5 ].

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.

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. By acting through four G-protein-coupled receptors, adenosine contributes critically to homeostasis and neuromodulatory control of a variety of normal and abnormal brain functions, ranging from synaptic plasticity, to cognition, to sleep, to motor activity to neuroinflammation, and cell death. This review begun with an overview of the gene and genome structure and the expression pattern of adenosine receptors ARs. We feature several new developments over the past decade in our understanding of AR functions in the brain, with special focus on the identification and characterization of canonical and noncanonical signaling pathways of ARs. We provide an update on functional insights from complementary genetic-knockout and pharmacological studies on the AR control of various brain functions.

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.

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A2B receptors mediate antimitogenesis in vascular smooth muscle cells. Psychostimulant addiction treatment. Treatment of A 1 receptors at room temperature with N-ethyl maleimide NEM , a free sulfhydryl modifying agent, does not affect antagonist binding, The influence of NEM on agonist binding is generally ascribed to an interaction with G i , not the ligand binding site. Blood Flow Metab. Role of adenosine receptor subtypes in methamphetamine reward and reinforcement. Dromotropic Refers to velocity of AV nodal conduction in the heart. Baumann, M. Activation of adenosine 2A receptors attenuates allograft rejection and alloantigen recognition. A 2B AR activation in human retinal endothelial cells stimulated neovascularization through production of vascular endothelial growth factor VEGF [ ]. Pingle, S. Some subjective effects consistent with stimulation were induced by SYN administration in cocaine users Lane et al. Merighi, S. Volpini, R.

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.

Varani, K. We suggest that efforts could be made in three main aspects of adenosine pharmacology affecting psychostimulant addiction. Modification of the rat adipocyte A1 adenosine receptor-adenylate cyclase system during chronic exposure to an A1 adenosine receptor agonist: Alterations in the quantity of GS alpha and Gi alpha are not associated with changes in their mRNAs. It has been shown in studies to inhibit some specific signal pathways of adenosine. Inhibition of adenosine uptake by ethanol is specific for one class of nucleoside transporters. Adenosine A1 and dopamine d1 receptor regulation of AMPA receptor phosphorylation and cocaine-seeking behavior. Meyerhof, W. Synapse 66, — Stenberg, D. A variety of A 2 -selective agonists have been found in in vivo testing to be much more A 2 -seiective than predicted in binding assays. Gene-targeting studies of mammalian behavior: is it the mutation or the background genotype?