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Nihon Yakurigaku Zasshi. Folia... Apr 2004Adenosine is thought to participate in the regulation of intraocular pressure since adenosine and several adenosine derivatives increase and/or decrease intraocular... (Review)
Review
Adenosine is thought to participate in the regulation of intraocular pressure since adenosine and several adenosine derivatives increase and/or decrease intraocular pressure. This article reviews the involvement of adenosine receptors in the regulation of intraocular pressure and the possible application of relatively selective adenosine A(2)-receptor agonists, 2-alkynyladenosine derivatives (2-AAs), as novel drugs for treatment of glaucoma. We found that some 2-AAs decreased intraocular pressure in normotensive rabbits. Moreover, these 2-AAs are also effective in the ocular hypertensive models induced by water-loading and alpha-chymotrypsin. In addition, the ocular hypotension induced by 2-(1-octyn-1-yl) derivative was inhibited by an adenosine A(2)-receptor antagonist 3,7-dimethyl-1-propargylxanthine, but not by an adenosine A(1) receptor antagonist 8-cyclopentyl-1,3-dipropyl xanthine. Moreover, the outflow facility was increased by the 2-(1-octyn-1-yl) derivative. These findings suggest that 2-AAs may affect intraocular pressure via adenosine A(2)-receptor, and 2-AAs-induced ocular hypotension is due to the increase in outflow facility. Some 2-AAs may be novel drugs against ocular hypertension and/or glaucoma, although additional studies are required to characterize the effects of 2-AAs on regulation of intraocular pressure in detail.
Topics: Adenosine; Adenosine A2 Receptor Agonists; Animals; Drug Design; Glaucoma; Humans; Intraocular Pressure; Ocular Hypertension; Phenethylamines; Rabbits; Receptors, Adenosine A2
PubMed: 15056945
DOI: 10.1254/fpj.123.289 -
Current Topics in Medicinal Chemistry 2003The search for potent and selective A(2A) adenosine receptor agonists has been particularly fruitful in the early nineties. A series of 2-amino, 2-alkoxy, 2-alkythio-,... (Review)
Review
The search for potent and selective A(2A) adenosine receptor agonists has been particularly fruitful in the early nineties. A series of 2-amino, 2-alkoxy, 2-alkythio-, 2-alkynyl-, and 2-alkenyl-derivatives of adenosine (Ado, 1) and N-ethylcarboxamidoadenosine (NECA, 30) have been synthesized and tested mainly on different model of rat A(1) and A(2A) receptor subtypes. From these studies some ligands, such as CGS 21680 (33), HENECA (42), and (S)-PHPNECA (46b), showed to possess high A(2A) affinity combined with good A(2A) vs A(1) selectivity. More detailed characterization of these ligands at the four cloned human adenosine receptor subtypes revealed that none of the prototypical adenosine receptor agonists exhibits at the same time high affinity and selectivity for the human A(2A)AR subtype. Both NECA and CGS 21680, which are avalaible as radioligands for this subtype, have lower affinity at human than at rat receptor. The 2-alkynylNECA derivatives HENECA an PHPNECA showed high affinity also at human A(3) receptors. In particular, (S)-PHPNECA displayed K(i)s in the low nanomolar range at A(1), A(2A), and A(3)subtypes and an EC(50) of 220 nM at human A(2B) receptor. On the other hand, it is now well known that the coronary vasodilation induced by Ado in different species is mediated by activation of A(2A)AR and a compound capable of producing coronary vasodilation through activation of A(2A)AR, but that is devoid of A(1)- and A(1)-agonist activity would have advantage over Ado for use in myocardial perfusion imaging studies. Other potential therapeutic applications of selective A(2A)AR agonists are as anti-aggregatory, anti-inflammatory, anti-psychotic, and anti-Huntington's disease agents. This review is aimed at presenting a complete overview of the medicinal chemistry development of A(2A) adenosine receptor agonists and at stressing the strong need for more selective ligands at A(2A) human subtype.
Topics: Adenosine; Animals; Drug Design; Humans; Ligands; Purinergic P1 Receptor Agonists; Receptor, Adenosine A2A; Structure-Activity Relationship
PubMed: 12570757
DOI: 10.2174/1568026033392282 -
European Journal of Pharmacology May 2008In situations of impending tissue danger, such as during ischaemia, the concentration of the endogenous purine nucleoside adenosine rapidly increases. Subsequent... (Review)
Review
In situations of impending tissue danger, such as during ischaemia, the concentration of the endogenous purine nucleoside adenosine rapidly increases. Subsequent stimulation of G-protein coupled adenosine receptors induces several cardiovascular effects, such as vasodilation, inhibition of inflammation, modulation of sympathetic nervous system activity, and increasing myocardial tolerance against ischaemia-reperfusion, which are all aimed at protecting the affected tissue. Although animal models have consistently shown profound cardiovascular protection by adenosine, up to now translation of this knowledge into clinical practice is limited. This current review is focused on human in vivo studies on the cardiovascular effects of adenosine. Several techniques, such as microdialysis, venous occlusion plethysmography, and (99m)Tc-annexin A5 scintigraphy can be used to study these effects of adenosine in healthy volunteers in vivo. By use of these techniques, recent studies have shown that the cardiovascular effects of adenosine can be modulated by genetic factors (e.g. a single nucleotide polymorphism in the gene encoding for adenosine monophosphate deaminase), by metabolic factors (e.g. by the plasma homocysteine concentration), and by drugs, such as caffeine, dipyridamole, and methotrexate. Given the cardiovascular protective properties of adenosine, these factors could well modulate the risk or extent of cardiovascular disease in patients and knowledge of these factors could be of benefit in daily clinical practice to optimize treatment in patients with cardiovascular disease.
Topics: Adenosine; Blood Vessels; Humans
PubMed: 18417123
DOI: 10.1016/j.ejphar.2008.01.053 -
Clinical Neuropharmacology Dec 1996After a review of the metabolism and pharmacology of adenosine, this work will examine the various therapeutic possibilities involving the use of agonists or antagonists... (Review)
Review
After a review of the metabolism and pharmacology of adenosine, this work will examine the various therapeutic possibilities involving the use of agonists or antagonists of adenosine A1 or A2 receptors in neurological disorders. Promising preclinical results have been obtained with epilepsy, cerebral ischemia, alcoholism, and pain.
Topics: Adenosine; Animals; Humans; Nervous System; Nervous System Physiological Phenomena; Purinergic P1 Receptor Agonists; Purinergic P1 Receptor Antagonists
PubMed: 8937786
DOI: 10.1097/00002826-199619060-00001 -
Chest Dec 1993
Review
Topics: Adenosine; Animals; Biomarkers; Cardiovascular Diseases; Humans
PubMed: 8252974
DOI: 10.1378/chest.104.6.1860 -
Bratislavske Lekarske Listy 2002Adenosine is an endogenous nucleoside that has been shown to be beneficial for the myocardium in different settings by a large number of experimental studies. In this... (Review)
Review
Adenosine is an endogenous nucleoside that has been shown to be beneficial for the myocardium in different settings by a large number of experimental studies. In this article, we 1) outline adenosine's metabolic pathways, 2) address cardioprotective properties of adenosine, and 3) discuss possible implications of the two recently published clinical studies disclosing a positive effect of adenosine monophosphate deaminase 1 (AMPD1) gene mutation on cardiovascular survival in heart failure and ischemic heart disease. (Fig. 2, Ref. 84.)
Topics: AMP Deaminase; Adenosine; Animals; Cardiovascular Diseases; Heart; Humans; Isoenzymes; Mutation; Survival Rate
PubMed: 12448564
DOI: No ID Found -
AdoR-1 (Adenosine Receptor) Contributes to Protection against Paraquat-Induced Oxidative Stress in .Oxidative Medicine and Cellular... 2022AdoR-1, the single adenosine receptor homolog in , which belongs to the superfamily of G-protein coupled receptors (GPCRs), mediates most of the physiological effects of...
AdoR-1, the single adenosine receptor homolog in , which belongs to the superfamily of G-protein coupled receptors (GPCRs), mediates most of the physiological effects of extracellular adenosine. Adenosine has been proved to improve the survival rate of in oxidative stress conditions. However, the potential mechanism of adenosine's protective effect against oxidative stress via AdoR-1 has not been studied. In this study, were divided into three groups: two groups with paraquat treatment, one in the presence and one in the absence of adenosine, and an untreated control group. Results indicate that many differentially expressed genes were found to be enriched significantly in neural-related signaling pathways among transcriptome data of three groups. Further gene network analysis showed that some important genes well known to be involved in promoting the acetylcholine release pathway, such as , , and and those involved in promoting the neuropeptide release pathway, such as were upregulated by paraquat induction but downregulated after adenosine treatment. Meanwhile, a completely opposite trend was observed for the gene that inhibits the acetylcholine-release and neuropeptide-release pathway. Additionally, some biochemical assays including SOD, GSSG, GSH, and AChE were measured to identify the potential protection of adenosine against oxidative stress between wild-type strain N2 and gene knockout strain EG6890. Conclusively, our study revealed series of adenosine receptor-mediated genes in that might act as regulators of paraquat-induced oxidative stress and may indicate adenosine's promising protective effects.
Topics: Animals; Caenorhabditis elegans; Paraquat; Caenorhabditis elegans Proteins; Acetylcholine; Oxidative Stress; Adenosine; Receptors, Purinergic P1
PubMed: 36589682
DOI: 10.1155/2022/1759009 -
Nature Reviews. Genetics Feb 2011Catalysed by members of the adenosine deaminase acting on RNA (ADAR) family of enzymes, adenosine-to-inosine (A-to-I) editing converts adenosines in RNA molecules to... (Review)
Review
Catalysed by members of the adenosine deaminase acting on RNA (ADAR) family of enzymes, adenosine-to-inosine (A-to-I) editing converts adenosines in RNA molecules to inosines, which are functionally equivalent to guanosines. Recently, global approaches to studying this widely conserved phenomenon have emerged. The use of bioinformatics, high-throughput sequencing and other approaches has increased the number of known editing sites by several orders of magnitude, and we now have a greater understanding of the control and the biological significance of editing. This Progress article reviews some of these recent global studies and their results.
Topics: Adenosine; Animals; Humans; Inosine; Nucleic Acid Conformation; RNA; RNA Editing
PubMed: 21173775
DOI: 10.1038/nrg2915 -
Canadian Journal of Physiology and... Mar 1995The present review describes the biological implications of the periodic changes of adenosine concentrations in different tissues of the rat. Adenosine is a purine... (Review)
Review
The present review describes the biological implications of the periodic changes of adenosine concentrations in different tissues of the rat. Adenosine is a purine molecule that could have been formed in the prebiotic chemical evolution and has been preserved. The rhythmicity of this molecule, as well as its metabolism and even the presence of specific receptors, suggests a regulatory role in eukaryotic cells and in multicellular organisms. Adenosine may be considered a chemical messenger and its action could take place at the level of the same cell (autocrine), the same tissue (paracrine), or on separate organs (endocrine). Exploration of the circadian variations of adenosine was planned considering the liver as an important tissue for purine formation, the blood as a vehicle among tissues, and the brain as the possible acceptor for hepatic adenosine or its metabolites. The rats used in these studies were adapted to a dark-light cycle of 12 h with an unrestrained feeding and drinking schedule. The metabolic control of adenosine concentration in the different tissues studied through the 24-h cycle is related to the activity of adenosine-metabolizing enzyme: 5'-nucleotidase adenosine deaminase, adenosine kinase, and S-adenosylhomocysteine hydrolase. Some possibilities of the factors modulating the activity of these enzymes are commented upon. The multiphysiological action of adenosine could be mediated by several actions: (i) by interaction with extracellular and intracellular receptors and (ii) through its metabolism modulating the methylation pathway, possibly inducing physiological lipoperoxidation, or participating in the energetic homeostasis of the cell. The physiological meaning of the circadian variations of adenosine and its metabolism was focused on: maintenance of the energetic homeostasis of the tissues, modulation of membrane structure and function, regulation of fasting and feeding metabolic pattern, and its participation in the sleep-wake cycle. From these considerations, we suggest that adenosine could be a molecular oscillator involved in the circadian pattern of biological activity in the rat.
Topics: Adenosine; Animals; Circadian Rhythm; Humans
PubMed: 7648513
DOI: 10.1139/y95-044 -
Acta Crystallographica. Section C,... Sep 2005In the title compound, 4-amino-1-(2-deoxy-beta-D-erythro-pentofuranosyl)-6-methylsulfanyl-1H-pyrazolo[3,4-d]pyrimidine, C11H16N5O3S, the conformation of the glycosidic...
In the title compound, 4-amino-1-(2-deoxy-beta-D-erythro-pentofuranosyl)-6-methylsulfanyl-1H-pyrazolo[3,4-d]pyrimidine, C11H16N5O3S, the conformation of the glycosidic bond is between anti and high anti. The 2'-deoxyribofuranosyl moiety adopts the C3'-exo-C4'-endo conformation (3T4, S-type sugar pucker), and the conformation at the exocyclic C-C bond is +sc (+gauche). The exocyclic 6-amine group and the 2-methylsulfanyl group lie on different sides of the heterocyclic ring system. The molecules form a three-dimensional hydrogen-bonded network that is stabilized by O-H...N, N-H...O and C-H...O hydrogen bonds.
Topics: Adenosine; Aza Compounds; Hydrogen Bonding; Models, Molecular
PubMed: 16143781
DOI: 10.1107/S0108270105024327