Abstract
Adenosine, the purine nucleoside, mediates its effects through activation of four G-protein coupled adenosine receptors (ARs) named as A1, A2A, A2B and A3. In particular, A1ARs are distributed through the body, primarily inhibitory in the regulation of adenylyl cyclase activity and able to reduce the cyclic AMP levels. Considerable advances have been made in the pharmacological and molecular characterization of A1ARs, which had been proposed as targets for the discovery and drug design of antagonists, agonists and allosteric enhancers. Several lines of evidence indicate that adenosine interacting with A1ARs may be an endogenous protective agent in the human body since it prevents the damage caused by various pathological conditions, such as in ischemia/hypoxia, epileptic seizures, excitotoxic neuronal injury and cardiac arrhythmias in cardiovascular system. It has also been reported that one of the most promising targets for the development of new anxiolytic drugs could be A1ARs, and that their activation may reduce pain signaling in the spinal cord. A1AR antagonists induce diuresis and natriuresis in various experimental models, mediating the inhibition of A1ARs in the proximal tubule which is primarily responsible for reabsorption and fluid uptake. In addition, the results of various studies indicate that adenosine is present within pancreatic islets and is implicated through A1ARs in the regulation of insulin secretion and in glucose concentrations. In the present paper it will become apparent that A1ARs could be implicated in the pharmacological treatment of several pathologies with an important influence on human health.
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Abbreviations
- AMP:
-
adenosine monophosphate
- AR:
-
Adenosine receptors
- cAMP:
-
cyclic adenosine monophosphate
- CNS:
-
central nervous system
- CREB-1:
-
cAMP responsive element binding protein 1
- HD:
-
Huntington’s disease
- TM:
-
transmembrane
References
Acton D, Miles GB (2015) Stimulation of glia reveals modulation of mammalian spinal motor networks by adenosine. PLoS One 10:e0134488
Akahane A, Katayama H, Mitsunaga T, Kato T, Kinoshita T, Kita Y, Kusunoki T, Terai T, Yoshida K, Shiokawa Y (1999) Discovery of 6-oxo-3-(2-phenylpyrazolo[1,5-a]pyridin-3-yl)-1(6H)- pyridazinebutanoic acid (FK 838): a novel non-xanthine adenosine A1 receptor antagonist with potent diuretic activity. J Med Chem 42:779–783
Albrecht-Küpper BE, Leineweber K, Nell PG (2012) Partial adenosine A1 receptor agonists for cardiovascular therapies. Purinergic Signal 8:91–99
Andersson O (2014) Role of adenosine signalling and metabolism in β-cell regeneration. Exp Cell Res 321:3–10
Antonioli L, Fornai M, Colucci R, Ghisu N, Tuccori M, Del Tacca M, Blandizzi C (2008) Regulation of enteric functions by adenosine: pathophysiological and pharmacological implications. Pharmacol Ther 120:233–253
Arrigoni E, Crocker AJ, Saper CB, Greene RW, Scammell TE (2005) Deletion of presynaptic adenosine A1 receptors impairs the recovery of synaptic transmission after hypoxia. Neuroscience 132:575–558
Ashton TD, Aumann KM, Baker SP, Schiesser CH, Scammells PJ (2007) Structure-activity relationships of adenosines with heterocyclic N6-substituents. Bioorg Med Chem Lett 1724:6779–6784
Aurora J, Manmohan S, Kenneth KH (2005) Pharmaceutical formulation for controlled release of selodenoson. WO patent 200525545, 24 mar 2005
Avila MY, Stone RA, Civan MM (2001) A1, A2A and A3 subtype adenosine receptors modulate intraocular pressure in the mouse. Br J Pharmacol 13:241–245
Baraldi PG, Zaid AN, Lampronti I, Fruttarolo F, Pavani MG, Tabrizi MA, Shryock JC, Leung E, Romagnoli R (2000) Synthesis and biological effects of a new series of 2-amino-3-benzoylthiophenes as allosteric enhancers of A1 adenosine receptor. Bioorg Med Chem Lett 10:1953–1957
Baraldi PG, Romagnoli R, Pavani MG, Nuñez Mdel C, Tabrizi MA, Shryock JC, Leung E, Moorman AR, Uluoglu C, Iannotta V, Merighi S, Borea PA (2003) Synthesis and biological effects of novel 2-amino-3-naphthoylthiophenes as allosteric enhancers of the A1 adenosine receptor. J Med Chem 46:794–809
Baraldi PG, Pavani MG, Shryock JC, Moorman AR, Iannotta V, Borea PA, Romagnoli R (2004) Synthesis of 2-amino-3-heteroaroylthiophenes and evaluation of their activity as potential allosteric enhancers at the human A1 receptor. Eur J Med Chem 39:855–865
Baraldi PG, Tabrizi MA, Gessi S, Borea PA (2008) Adenosine receptor antagonists: translating medicinal chemistry and pharmacology into clinical utility. Chem Rev 108:238–263
Barth S, Nesper J, Hasgall PA, Wirthner R, Nytko KJ, Edlich F, Katschinski DM, Stiehl DP, Wenger RH, Camenisch G (2007) The peptidyl prolyl cis/trans isomerase FKBP38 determines hypoxia-inducible transcription factor prolyl-4-hydroxylase PHD2 protein stability. Mol Cell Biol 27:3758–3768
Basheer R, Arrigoni E, Thatte HS, Greene RW, Ambudkar IS, McCarley RW (2002) Adenosine induces inositol 1,4,5-trisphosphate receptor-mediated mobilization of intracellular calcium stores in basal forebrain cholinergic neurons. J Neurosci 22:7680–7686
Belibi FA, Wallace DP, Yamaguchi T, Christensen M, Reif G, Grantham JJ (2002) The effect of caffeine on renal epithelial cells from patients with autosomal dominant polycystic kidney disease. J Am Soc Nephrol 13:2723–2729
Bell TD, Luo Z, Welch WJ (2010) Glomerular tubular balance is suppressed in adenosine type 1 receptor-deficient mice. Am J Physiol Renal Physiol 299:F1158–F1163
Berman RF, Fredholm BB, Aden U, O’Connor WT (2000) Evidence for increased dorsal hippocampal adenosine release and metabolism during pharmacologically induced seizures in rats. Brain Res 872:44–53
Biber K, Klotz KN, Berger M, Gebicke-Härter PJ, van Calker D (1997) Adenosine A1 receptor-mediated activation of phospholipase C in cultured astrocytes depends on the level of receptor expression. J Neurosci 17:4956–4964
Björck T, Gustafsson LE, Dahlén SE (1992) Isolated bronchi from asthmatics are hyperresponsive to adenosine, which apparently acts indirectly by liberation of leukotrienes and histamine. Am Rev Respir Dis 145:1087–1091
Boden G (2003) Effects of free fatty acids (FFA) on glucose metabolism: significance for insulin resistance and type 2 diabetes. Exp Clin Endocrinol Diabetes 111:121–124
Böhm M, Pieske B, Ungerer M, Erdmann E (1989) Characterization of A1 adenosine receptors in atrial and ventricular myocardium from diseased human hearts. Circ Res 65:1201–1211
Bøhn SK, Ward NC, Hodgson JM, Croft KD (2012) Effects of tea and coffee on cardiovascular disease risk. Food Funct 3:575–591
Boison D (2008) The adenosine kinase hypothesis of epileptogenesis. Prog Neurobiol 84:249–262
Borea PA, Varani K, Vincenzi F, Baraldi PG, Tabrizi MA, Merighi S, Gessi S (2015) The A3 adenosine receptor: history and perspectives. Pharmacol Rev 67:74–102
Borea PA, Gessi S, Merighi S, Varani K (2016) Adenosine as a multi-signalling guardian angel in human diseases: when, where and how does it exert its protective effects? Trends Pharmacol Sci 37:419–434
Boros D, Thompson J, Larson DF (2016) Adenosine regulation of the immune response initiated by ischemia reperfusion injury. Perfusion 31:103–110
Bours MJ, Swennen EL, Di Virgilio F, Cronstein BN, Dagnelie PC (2006) Adenosine 5′-triphosphate and adenosine as endogenous signaling molecules in immunity and inflammation. Pharmacol Ther 112:358–404
Braas KM, Zarbin MA, Snyder SH (1987) Endogenous adenosine and adenosine receptors localized to ganglion cells of the retina. Proc Natl Acad Sci U S A 84:3906–3910
Brito R, Pereira MR, Paes-de-Carvalho R, Calaza Kda C (2012) Expression of A1 adenosine receptors in the developing avian retina: in vivo modulation by A2A receptors and endogenous adenosine. J Neurochem 123:239–249
Brown RA, Clarke GW, Ledbetter CL, Hurle MJ, Denyer JC, Simcock DE, Coote JE, Savage TJ, Murdoch RD, Page CP, Spina D, O’Connor BJ (2008) Elevated expression of adenosine A1 receptor in bronchial biopsy specimens from asthmatic subjects. Eur Respir J 31:311–319
Bruns RF, Fergus JH (1990) Allosteric enhancement of adenosine A1 receptor binding and function by 2-amino-3-benzoylthiophenes. Mol Pharmacol 38:939–949
Burgdorf C, Richardt D, Kurz T, Seyfarth M, Jain D, Katus HA, Richardt G (2001) Adenosine inhibits norepinephrine release in the postischemic rat heart: the mechanism of neuronal stunning. Cardiovasc Res 49:713–720
Burnstock G (2011) Introductory overview of purinergic signalling. Front Biosci 3:896–900
Burnstock G (2013) Introduction to purinergic signalling in the brain. Adv Exp Med Biol 986:1–12
Burnstock G (2014) Purinergic signalling in the gastrointestinal tract and related organs in health and disease. Purinergic Signal 10:3–50
Burnstock G, Pelleg A (2015) Cardiac purinergic signalling in health and disease. Purinergic Signal 11:1–46
Burnstock G, Brouns I, Adriaensen D, Timmermans JP (2012) Purinergic signaling in the airways. Pharmacol Rev 64:834–868
Burnstock G, Evans LC, Bailey MA (2014) Purinergic signalling in the kidney in health and disease. Purinergic Signal 10:71–101
Butcher A, Scammells PJ, White PJ, Devine SM, Rose’meyer RB (2013) An allosteric modulator of the adenosine A1 receptor improves cardiac function following ischaemia in murine isolated hearts. Pharmaceuticals (Basel) 6:546–556
Camici M, Micheli V, Ipata PL, Tozzi MG (2010) Pediatric neurological syndromes and inborn errors of purine metabolism. Neurochem Int 56:367–378
Canals M, Lane JR, Wen A, Scammells PJ, Sexton PM, Christopoulos A (2012) A Monod-Wyman-Changeux mechanism can explain G protein-coupled receptor (GPCR) allosteric modulation. J Biol Chem 287:650–659
Cappellacci L, Franchetti P, Vita P, Petrelli R, Lavecchia A, Costa B, Spinetti F, Martini C, Klotz KN, Grifantini M (2008) 5′-Carbamoyl derivatives of 2′-C-methyl-purine nucleosides as selective A1 adenosine receptor agonists: affinity, efficacy, and selectivity for A1 receptor from different species. Bioorg Med Chem 16:336–353
Carlin JL, Jain S, Gizewski E, Wan TC, Tosh DK, Xiao C, Auchampach JA, Jacobson KA, Gavrilova O, Reitman ML (2017) Hypothermia in mouse is caused by adenosine A1 and A3 receptor agonists and AMP via three distinct mechanisms. Neuropharmacology 114:101–113
Carrettiero DC, Almeida RS, Fior-Chadi DR (2008) Adenosine modulates alpha2-adrenergic receptors within specific subnuclei of the nucleus tractus solitarius in normotensive and spontaneously hypertensive rats. Hypertens Res 31:2177–2186
Carrettiero DC, da Silva SM, Fior-Chadi DR (2009) Adenosine modulates alpha2-adrenergic receptors through a phospholipase C pathway in brainstem cell culture of rats. Auton Neurosci 151:174–177
Chandra R, Liddle RA (2014) Recent advances in the regulation of pancreatic secretion. Curr Opin Gastroenterol 30:490–494
Chandrasekera PC, Wan TC, Gizewski ET, Auchampach JA, Lasley RD (2013) Adenosine A1 receptors heterodimerize with β1- and β2-adrenergic receptors creating novel receptor complexes with altered G protein coupling and signaling. Cell Signal 25:736–742
Chang LC, Brussee J, Ijzerman AP (2004a) Non-xanthine antagonists for the adenosine A1 receptor. Chem Biodivers 1:1591–1626
Chang LC, Spanjersberg RF, von Frijtag Drabbe Künzel JK, Mulder-Krieger T, van den Hout G, Beukers MW, Brussee J, Ijzerman AP (2004b) 2,4,6-trisubstituted pyrimidines as a new class of selective adenosine A1 receptor antagonists. J Med Chem 47:6529–6540
Chang LC, von Frijtag Drabbe Künzel JK, Mulder-Krieger T, Westerhout J, Spangenberg T, Brussee J, Ijzerman AP (2007) 2,6,8-trisubstituted 1-deazapurines as adenosine receptor antagonists. J Med Chem 50:828–834
Chen JF, Eltzschig HK, Fredholm BB (2013) Adenosine receptors as drug targets--what are the challenges? Nat Rev Drug Discov 12:265–286
Cheng JT, Chi TC, Liu IM (2000) Activation of adenosine A1 receptors by drugs to lower plasma glucose in streptozotocin-induced diabetic rats. Auton Neurosci 83:127–133
Cheung JW, Lerman BB (2003) CVT-510: a selective A1 adenosine receptor agonist. Cardiovasc Drug Rev 21:277–292
Childers SR, Li X, Xiao R, Eisenach JC (2005) Allosteric modulation of adenosine A1 receptor coupling to G-proteins in brain. J Neurochem 93:715–723
Christofi FL, Zhang H, Yu JG, Guzman J, Xue J, Kim M, Wang YZ, Cooke HJ (2001) Differential gene expression of adenosine A1, A2A, A2B, and A3 receptors in the human enteric nervous system. J Comp Neurol 439:46–64
Christofi FL, Kim M, Wunderlich JE, Xue J, Suntres Z, Cardounel A, Javed NH, Yu JG, Grants I, Cooke HJ (2004) Endogenous adenosine differentially modulates 5-hydroxytryptamine release from a human enterochromaffin cell model. Gastroenterology 127:188–202
Christopoulos A (2002) Allosteric binding sites on cell-surface receptors: novel targets for drug discovery. Nat Rev Drug Discov 1:198–210
Cieślak M, Wojtczak A, Komoszyński M (2016) Role of the purinergic signaling in epilepsy. Pharmacol Rep 69:130–138
Ciruela F, Casadó V, Rodrigues RJ, Luján R, Burgueño J, Canals M, Borycz J, Rebola N, Goldberg SR, Mallol J, Cortés A, Canela EI, López-Giménez JF, Milligan G, Lluis C, Cunha RA, Ferré S, Franco R (2006) Presynaptic control of striatal glutamatergic neurotransmission by adenosine A1-A2A receptor heteromers. J Neurosci 26(7):2080–2087
Coelho JE, Rebola N, Fragata I, Ribeiro JA, de Mendonça A, Cunha RA (2006) Hypoxia-induced desensitization and internalization of adenosine A1 receptors in the rat hippocampus. Neuroscience 138:1195–1203
Cooke HJ, Wang Y, Liu CY, Zhang H, Christofi FL (1999) Activation of neuronal adenosine A1 receptors suppresses secretory reflexes in the guinea pig colon. Am J Phys 276:G451–G462
Cronstein BN, Levin RI, Philips M, Hirschhorn R, Abramson SB, Weissmann G (1992) Neutrophil adherence to endothelium is enhanced via adenosine A1 receptors and inhibited via adenosine A2 receptors. J Immunol 148:2201–2206
Crosson CE (2001) Intraocular pressure responses to the adenosine agonist cyclohexyladenosine: evidence for a dual mechanism of action. Invest Ophthalmol Vis Sci 42:1837–1840
Cunha RA (2008) Caffeine, adenosine receptors, memory and Alzheimer disease. Med Clin (Barc) 131:790–795
Cunha RA (2016) How does adenosine control neuronal dysfunction and neurodegeneration? J Neurochem 139:1019–1055
Daly JW, Padgett WL, Secunda SI, Thompson RD, Olsson RA (1993) Structure-activity relationships for 2-substituted adenosines at A1 and A2 adenosine receptors. Pharmacology 46:91–100
de Mendonça A, Sebastião AM, Ribeiro JA (2000) Adenosine: does it have a neuroprotective role after all? Brain Res Brain Res Rev 33:258–274
Dhalla AK, Wong MY, Voshol PJ, Belardinelli L, Reaven GM (2007a) A1 adenosine receptor partial agonist lowers plasma FFA and improves insulin resistance induced by high-fat diet in rodents. Am J Physiol Endocrinol Metab 292:E1358–E1363
Dhalla AK, Santikul M, Smith M, Wong MY, Shryock JC, Belardinelli L (2007b) Antilipolytic activity of a novel partial A1 adenosine receptor agonist devoid of cardiovascular effects: comparison with nicotinic acid. J Pharmacol Exp Ther 321:327–333
Dhalla AK, Chisholm JW, Reaven GM, Belardinelli L (2009) A1 adenosine receptor: role in diabetes and obesity. Handb Exp Pharmacol 193:271–295
Dittrich HC, Gupta DK, Hack TC, Dowling T, Callahan J, Thomson S (2007) The effect of KW-3902, an adenosine A1 receptor antagonist, on renal function and renal plasma flow in ambulatory patients with heart failure and renal impairment. J Card Fail 13:609–617
Doggrell SA (2005) BG-9928 (Biogen Idec). Curr Opin Investig Drugs 6:962–968
Dong Q, Ginsberg HN, Erlanger BF (2001) Overexpression of the A1 adenosine receptor in adipose tissue protects mice from obesity-related insulin resistance. Diabetes Obes Metab 3:360–366
Duarte JM, Carvalho RA, Cunha RA, Gruetter R (2009) Caffeine consumption attenuates neurochemical modifications in the hippocampus of streptozotocin-induced diabetic rats. J Neurochem 111:368–379
Edwards JM, Alloosh MA, Long XL, Dick GM, Lloyd PG, Mokelke EA, Sturek M (2008) Adenosine A1 receptors in neointimal hyperplasia and in-stent stenosis in Ossabaw miniature swine. Coron Artery Dis 19:27–31
El Yacoubi M, Ledent C, Parmentier M, Costentin J, Vaugeois JM (2000) The anxiogenic-like effect of caffeine in two experimental procedures measuring anxiety in the mouse is not shared by selective A2A adenosine receptor antagonists. Psychopharmacol (Berl) 148:153–163
Ellis MJ, Lindon AC, Flint KJ, Jones NC, Goodbourn S (1995) Activating transcription factor-1 is a specific antagonist of the cyclic adenosine 3′.5′-monophosphate (cAMP) response element-binding protein-1-mediated response to cAMP. Mol Endocrinol 9:255–265
Elzein E, Kalla R, Li X, Perry T, Marquart T, Micklatcher M, Li Y, Wu Y, Zeng D, Zablocki J (2007) N6-Cycloalkyl-2-substituted adenosine derivatives as selective, high affinity adenosine A1 receptor agonists. Bioorg Med Chem Lett 17:161–166
Ethier MF, Madison JM (2006) Adenosine A1 receptors mediate mobilization of calcium in human bronchial smooth muscle cells. Am J Respir Cell Mol Biol 35:496–502
Ezeamuzie CI, Philips E (1999) Adenosine A3 receptors on human eosinophils mediate inhibition of degranulation and superoxide anion release. Br J Pharmacol 127:188–194
Fastbom J, Pazos A, Probst A, Palacios JM (1986) Adenosine A1 receptors in human brain: characterization and autoradiographic visualization. Neurosci Lett 65:127–132
Fastbom J, Pazos A, Palacios JM (1987) The distribution of adenosine A1 receptors and 5′-nucleotidase in the brain of some commonly used experimental animals. Neurosci 22:813–826
Ferrante A, Martire A, Pepponi R, Varani K, Vincenzi F, Ferraro L, Beggiato S, Tebano MT, Popoli P (2014) Expression, pharmacology and functional activity of adenosine A1 receptors in genetic models of Huntington’s disease. Neurobiol Dis 71:193–204
Ferré S, Ciruela F, Quiroz C, Luján R, Popoli P, Cunha RA, Agnati LF, Fuxe K, Woods AS, Lluis C, Franco R (2007) Adenosine receptor heteromers and their integrative role in striatal function. Sci World J 7:74–85
Franchetti P, Cappellacci L, Vita P, Petrelli R, Lavecchia A, Kachler S, Klotz KN, Marabese I, Luongo L, Maione S, Grifantini M (2009) N6-Cycloalkyl- and N6-bicycloalkyl-C5′(C2′)-modified adenosine derivatives as high-affinity and selective agonists at the human A1 adenosine receptor with antinociceptive effects in mice. J Med Chem 52:2393–2406
Fredholm BB, Arslan G, Halldner L, Kull B, Schulte G, Wasserman W (2000) Structure and function of adenosine receptors and their genes. Naunyn Schmiedeberg’s Arch Pharmacol 362:364–374
Fredholm BB, IJzerman AP, Jacobson KA, Linden J, Müller CE (2011a) International Union of Basic and Clinical Pharmacology. LXXXI. Nomenclature and classification of adenosine receptors an update. Pharmacol Rev 63:1–34
Fredholm BB, IJzerman AP, Jacobson KA, Linden J, Müller CE (2011b) International Union of Basic and Clinical Pharmacology. LXXXI. Nomenclature and classification of adenosine receptors-an update. Pharmacol Rev 63:1–34
Fredholm BB, Johansson S, Wang YQ (2011c) Adenosine and the regulation of metabolism and body temperature. Adv Pharmacol 61:77–94
Fredholm BB, Yang J, Wang Y (2016) Low, but not high, dose caffeine is a readily available probe for adenosine actions. Mol Asp Med S0098-2997:30080–30082
Funakoshi H, Chan TO, Good JC, Libonati JR, Piuhola J, Chen X, MacDonnell SM, Lee LL, Herrmann DE, Zhang J, Martini J, Palmer TM, Sanbe A, Robbins J, Houser SR, Koch WJ, Feldman AM (2006) Regulated overexpression of the A1 adenosine receptor in mice results in adverse but reversible changes in cardiac morphology and function. Circulation 114:2240–2250
Gao ZG, Jacobson KA (2007) Emerging adenosine receptor agonists. Expert Opin Emerg Drugs 12:479–492
Gao ZG, Jacobson KA (2011) Emerging adenosine receptor agonists: an update. Expert Opin Emerg Drugs 16:597–602
Gao ZG, Melman N, Erdmann A, Kim SG, Müller CE, IJzerman AP, Jacobson KA (2003) Differential allosteric modulation by amiloride analogues of agonist and antagonist binding at A1 and A3 adenosine receptors. Biochem Pharmacol 65:525–534
Gao ZG, Kim SK, Ijzerman AP, Jacobson KA (2005) Allosteric modulation of the adenosine family of receptors. Mini Rev Med Chem 5:545–553
Gergs U, Boknik P, Schmitz W, Simm A, Silber RE, Neumann J (2009) A positive inotropic effect of adenosine in cardiac preparations of right atria from diseased human hearts. Naunyn Schmiedeberg’s Arch Pharmacol 379:533–540
Gessi S, Merighi S, Fazzi D, Stefanelli A, Varani K, Borea PA (2011) Adenosine receptor targeting in health and disease. Expert Opin Investig Drugs 20:1591–1609
Gessi S, Merighi S, Stefanelli A, Fazzi D, Varani K, Borea PA (2013) A1 and A3 adenosine receptors inhibit LPS-induced hypoxia-inducible factor-1 accumulation in murine astrocytes. Pharmacol Res 76:157–170
Giménez-Llort L, Fernández-Teruel A, Escorihuela RM, Fredholm BB, Tobeña A, Pekny M, Johansson B (2002) Mice lacking the adenosine A1 receptor are anxious and aggressive, but are normal learners with reduced muscle strength and survival rate. Eur J Neurosci 16:547–550
Ginés S, Hillion J, Torvinen M, Le Crom S, Casadó V, Canela EI, Rondin S, Lew JY, Watson S, Zoli M, Agnati LF, Verniera P, Lluis C, Ferré S, Fuxe K, Franco R (2000) Dopamine D1 and adenosine A1 receptors form functionally interacting heteromeric complexes. Proc Natl Acad Sci U S A 97:8606–8611
Giordanetto F, Fossa P, Menozzi G, Schenone S, Bondavalli F, Ranise A, Mosti L (2003) Exploring the molecular basis of selectivity in A1 adenosine receptors agonists: a case study. J Comput Aided Mol Des 17:39–51
Giorgi I, Nieri P (2013) Adenosine A1 modulators: a patent update (2008 to present). Expert Opin Ther Pat 23:1109–1121
Givertz MM, Massie BM, Fields TK, Pearson LL, Dittrich HC (2007) The effects of KW-3902, an adenosine A1 receptor antagonist, on diuresis and renal function in patients with acute decompensated heart failure and renal impairment or diuretic resistance. J Am Coll Cardiol 50:1551–1560
Gomes WA, Shinnar S (2011) Prospects for imaging-related biomarkers of human epileptogenesis: a critical review. Biomark Med 5:599–606
Gomes CV, Kaster MP, Tomé AR, Agostinho PM, Cunha RA (2011) Adenosine receptors and brain diseases: neuroprotection and neurodegeneration. Biochim Biophys Acta 1808:1380–1399
Goodman RR, Synder SH (1982) Autoradiographic localization of adenosine receptors in rat brain using [3H]cyclohexyladenosine. J Neurosci 2:1230–1241
Gouder N, Fritschy JM, Boison D (2003) Seizure suppression by adenosine A1 receptor activation in a mouse model of pharmacoresistant epilepsy. Epilepsia 44:877–885
Grden M, Podgorska M, Kocbuch K, Szutowicz A, Pawelczyk T (2006) Expression of adenosine receptors in cardiac fibroblasts as a function of insulin and glucose level. Arch Biochem Biophys 455:10–17
Greenberg B, Thomas I, Banish D, Goldman S, Havranek E, Massie BM, Zhu Y, Ticho B, Abraham WT (2007) Effects of multiple oral doses of an A1 adenosine antagonist, BG9928, in patients with heart failure: results of a placebo-controlled, dose-escalation study. J Am Coll Cardiol 50:600–606
Grewal SS, Fass DM, Yao H, Ellig CL, Goodman RH, Stork PJ (2000) Calcium and cAMP signals differentially regulate cAMP-responsive element-binding protein function via a Rap1-extracellular signal-regulated kinase pathway. J Biol Chem 275:34433–34441
Hansen PB, Schnermann J (2003) Vasoconstrictor and vasodilator effects of adenosine in the kidney. Am J Physiol Renal Physiol 285:F590–F599
Hartwick AT, Lalonde MR, Barnes S, Baldridge WH (2004) Adenosine A1 receptor modulation of glutamate-induced calcium influx in rat retinal ganglion cells. Invest Ophthalmol Vis Sci 45:3740–3748
Headrick JP, Hack B, Ashton KJ (2003) Acute adenosinergic cardioprotection in ischemic-reperfused hearts. Am J Physiol Heart Circ Physiol 285:H1797–H1818
Headrick JP, Ashton KJ, Rose’meyer RB, Peart JN (2013) Cardiovascular adenosine receptors: expression, actions and interactions. Pharmacol Ther 140:92–111
Heller AR, Rothermel J, Weigand MA, Plaschke K, Schmeck J, Wendel M, Bardenheuer HJ, Koch T (2007) Adenosine A1 and A2 receptor agonists reduce endotoxin-induced cellular energy depletion and oedema formation in the lung. Eur J Anaesthesiol 24:258–266
Hodges RR, Dartt DA (2016) Signaling pathways of Purinergic receptors and their interactions with cholinergic and adrenergic pathways in the lacrimal gland. J Ocul Pharmacol Ther 32:490–497
Hua X, Erikson CJ, Chason KD, Rosebrock CN, Deshpande DA, Penn RB, Tilley SL (2007) Involvement of A1 adenosine receptors and neural pathways in adenosine-induced bronchoconstriction in mice. Am J Physiol Lung Cell Mol Physiol 29:L25–L32
Husain S, Shearer TW, Crosson CE (2007) Mechanisms linking adenosine A1 receptors and extracellular signal-regulated kinase 1/2 activation in human trabecular meshwork cells. J Pharmacol Exp Ther 320:258–265
Hussain T, Mustafa SJ (1995) Binding of A1 adenosine receptor ligand [3H] 8-cyclopentyl-1,3-dipropylxanthine in coronary smooth muscle. Circ Res 77:194–198
Ivanov AA, Palyulin VA, Zefirov NS (2007) Computer aided comparative analysis of the binding modes of the adenosine receptor agonists for all known subtypes of adenosine receptors. J Mol Graph Model 25:740–754
Jaberi E, Rohani M, Shahidi GA, Nafissi S, Arefian E, Soleimani M, Moghadam A, Arzenani MK, Keramatian F, Klotzle B, Fan JB, Turk C, Steemers F, Elahi E (2016) Mutation in ADORA1 identified as likely cause of early-onset parkinsonism and cognitive dysfunction. Mov Disord 31:1004–1011
Jacobson KA, Civan MM (2016) Ocular purine receptors as drug targets in the eye. J Ocul Pharmacol Ther 32:534–547
Jacobson KA, Gao ZG (2006) Adenosine receptors as therapeutic targets. Nat Rev Drug Discov 5:247–264
Johansson B, Halldner L, Dunwiddie TV, Masino SA, Poelchen W, Giménez-Llort L, Escorihuela RM, Fernández-Teruel A, Wiesenfeld-Hallin Z, Xu XJ, Hårdemark A, Betsholtz C, Herlenius E, Fredholm BB (2001) Hyperalgesia, anxiety, and decreased hypoxic neuroprotection in mice lacking the adenosine A1 receptor. Proc Natl Acad Sci U S A 98:9407–9412
Johansson SM, Salehi A, Sandström ME, Westerblad H, Lundquist I, Carlsson PO, Fredholm BB, Katz A (2007a) A1 receptor deficiency causes increased insulin and glucagon secretion in mice. Biochem Pharmacol 74:1628–1635
Johansson SM, Yang JN, Lindgren E, Fredholm BB (2007b) Eliminating the antilipolytic adenosine A1 receptor does not lead to compensatory changes in the antilipolytic actions of PGE2 and nicotinic acid. Acta Physiol (Oxf) 190:87–96
Johansson SM, Lindgren E, Yang JN, Herling AW, Fredholm BB (2008) Adenosine A1 receptors regulate lipolysis and lipogenesis in mouse adipose tissue-interactions with insulin. Eur J Pharmacol 597:92–101
Kadowaki M, Tokita K, Nagakura Y, Takeda M, Hanaoka K, Tomoi M (2000) Adenosine A1 receptor blockade reverses dysmotility induced by ischemia-reperfusion in rat colon. Eur J Pharmacol 409:319–323
Kalk P, Eggert B, Relle K, Godes M, Heiden S, Sharkovska Y, Fischer Y, Ziegler D, Bielenberg GW, Hocher B (2007) The adenosine A1 receptor antagonist SLV320 reduces myocardial fibrosis in rats with 5/6 nephrectomy without affecting blood pressure. Br J Pharmacol 151:1025–1032
Kapicka CL, Montamat SC, Olson RD, Musser B, Mudumbi RV, Vestal RE (2003) Species comparison of adenosine A1 receptors in isolated mammalian atrial and ventricular myocardium. Life Sci 72:2825–2838
Kaplan JL, Gao E, De Garavilla L, Victain M, Minczak B, Dalsey WC (2003) Adenosine A1 antagonism attenuates atropine-resistant hypoxic bradycardia in rats. Acad Emerg Med 10:923–930
Ke JJ, Yu FX, Rao Y, Wang YL (2011) Adenosine postconditioning protects against myocardial ischemia-reperfusion injury though modulate production of TNF-α and prevents activation of transcription factor NF-kappaB. Mol Biol Rep 38:531–538
Keir S, Boswell-Smith V, Spina D, Page C (2006) Mechanism of adenosine-induced airways obstruction in allergic guinea pigs. Br J Pharmacol 147:720–728
Khan RB, Yerremsetty PK, Lindstrom D, McGill LJ (2001) Emergency EEG and factors associated with nonconvulsive status epilepticus. J Natl Med Assoc 93:359–362
Kieć-Kononowicz K, Drabczyńska A, Pękala E, Michalak B, Müller CE, Schumacher B, Karolak-Wojciechowska J, Duddeck H, Rockitt S, Wartchow R (2001) New developments in A1 and A2 adenosine receptor antagonists. Pure App Chem 73:1411–1420
Kiesman WF, Zhao J, Conlon PR, Petter RC, Jin X, Smits G, Lutterodt F, Sullivan GW, Linden J (2006) Norbornyllactone-substituted xanthines as adenosine A1 receptor antagonists. Bioorg Med Chem 14:3654–3661
Kiesman WF, Elzein E, Zablocki J (2009) A1 adenosine receptor antagonists, agonists, and allosteric enhancers. Handb Exp Pharmacol 193:25–58
Kirkup AJ, Brunsden AM, Grundy D (2001) Receptors and transmission in the brain-gut axis: potential for novel therapies. I. Receptors on visceral afferents. Am J Physiol Gastrointest Liver Physiol 280:G787–G794
Klinger M, Freissmuth M, Nanoff C (2002) Adenosine receptors: G protein-mediated signalling and the role of accessory proteins. Cell Signal 14:99–108
Klotz KN, Hessling J, Hegler J, Owman C, Kull B, Fredholm BB, Lohse MJ (1998) Comparative pharmacology of human adenosine receptor subtypes - characterization of stably transfected receptors in CHO cells. Naunyn Schmiedeberg’s Arch Pharmacol 357:1–9
Kohno Y, Nagatomi I, Hanaoka K (1993) Pyrazolopyridine compounds for the treatment of anemia. WO patent 1993025205, 23 dec 1993
Kolachala VL, Bajaj R, Chalasani M, Sitaraman SV (2008) Purinergic receptors in gastrointestinal inflammation. Am J Physiol Gastrointest Liver Physiol 294:G401–G410
Kunduri S, Dick G, Nayeem M, Mustafa S (2013) Adenosine A1 receptor signaling inhibits BK channels through a PKCα-dependent mechanism in mouse aortic smooth muscle. Physiol Rep 1:e00037
Lancelot E, Idée JM, Laclédère C, Santus R, Corot C (2002) Effects of two dimeric iodinated contrast media on renal medullary blood perfusion and oxygenation in dogs. Investig Radiol 37:368–375
Lang UE, Lang F, Richter K, Vallon V, Lipp HP, Schnermann J, Wolfer DP (2003) Emotional instability but intact spatial cognition in adenosine receptor 1 knock out mice. Behav Brain Res 145:179–188
Larrouy D, Galitzky J, Lafontan M (1991) A1 adenosine receptors in the human fat cell: tissue distribution and regulation of radioligand binding. Eur J Pharmacol 206:139–147
Lazarowski ER, Boucher RC, Harden TK (2000) Constitutive release of ATP and evidence for major contribution of ecto-nucleotide pyrophosphatase and nucleoside diphosphokinase to extracellular nucleotide concentrations. J Biol Chem 275:31061–31068
Lee JJ, Parsons ME (2000) Signaling mechanisms coupled to presynaptic A1 and H3 receptors in the inhibition of cholinergic contractile responses of the guinea pig ileum. J Pharmacol Exp Ther 295:607–613
Lee JJ, Talubmook C, Parsons ME (2001) Activation of presynaptic A1 receptors by endogenous adenosine inhibits acetylcholine release in the guinea-pig ileum. J Auton Pharmacol 21:29–38
Lee HK, Choi SS, Han KJ, Han EJ, Suh HW (2004) Roles of adenosine receptors in the regulation of kainic acid-induced neurotoxic responses in mice. Brain Res Mol Brain Res 125:76–85
Lee DL, Bell TD, Bhupatkar J, Solis G, Welch WJ (2012) Adenosine A1 receptor knockout mice have a decreased blood pressure response to low-dose ANG II infusion. Am J Physiol Regul Integr Comp Physiol 303:R683–R688
Li X, Conklin D, Ma W, Zhu X, Eisenach JC (2002) Spinal noradrenergic activation mediates allodynia reduction from an allosteric adenosine modulator in a rat model of neuropathic pain. Pain 97:117–125
Li X, Conklin D, Pan HL, Eisenach JC (2003) Allosteric adenosine receptor modulation reduces hypersensitivity following peripheral inflammation by a central mechanism. J Pharmacol Exp Ther 305:950–955
Li T, Quan Lan J, Fredholm BB, Simon RP, Boison D (2007) Adenosine dysfunction in astrogliosis: cause for seizure generation? Neuron Glia Biol 3:353–366
Li A, Leung CT, Peterson-Yantorno K, Stamer WD, Mitchell CH, Civan MM (2012) Mechanisms of ATP release by human trabecular meshwork cells, the enabling step in purinergic regulation of aqueous humor outflow. J Cell Physiol 227:172–182
Li RH, Ding CK, Jiang YN, Ding ZC, An XM, Tang HT, Jing QW, Zhan ZP (2016) Synthesis of 5,6-Dihydropyrazolo[5,1-a]isoquinolines through indium(III)-promoted Halocyclizations of N-Propargylic Sulfonylhydrazones. Org Lett 18:1666–1669
Lopes LV, Sebastião AM, Ribeiro JA (2011) Adenosine and related drugs in brain diseases: present and future in clinical trials. Curr Top Med Chem 11:1087–1101
Lütjens H, Zickgraf A, Figler H, Linden J, Olsson RA, Scammells PJ (2003) 2-amino-3-benzoylthiophene allosteric enhancers of A1 adenosine agonist binding: new 3, 4-, and 5-modifications. J Med Chem 46:1870–1877
Lynch JJ, Alexander KM, Jarvis MF, Kowaluk EA (1998) Inhibition of adenosine kinase during oxygen-glucose deprivation in rat cortical neuronal cultures. Neurosci Lett 252:207–210
Lynge J, Hellsten Y (2000) Distribution of adenosine A1, A2A and A2B receptors in human skeletal muscle. Acta Physiol Scand 169:283–290
Maione S, de Novellis V, Cappellacci L, Palazzo E, Vita D, Luongo L, Stella L, Franchetti P, Marabese I, Rossi F, Grifantini M (2007) The antinociceptive effect of 2-chloro-2′-C-methyl-N6-cyclopentyladenosine (2′-me-CCPA), a highly selective adenosine A1 receptor agonist, in the rat. Pain 131:281–292
Mansourian S, Bina P, Fehri A, Karimi AA, Boroumand MA, Abbasi K (2015) Preoperative oral pentoxifylline in case of coronary artery bypass grafting with left ventricular dysfunction (ejection fraction equal to/less than 30%). Anatol J Cardiol 15:1014–1019
McNamara N, Gallup M, Khong A, Sucher A, Maltseva I, Fahy J, Basbaum C (2004) Adenosine up-regulation of the mucin gene, MUC2, in asthma. FASEB J 18:1770–1772
Merighi S, Borea PA, Stefanelli A, Bencivenni S, Castillo CA, Varani K, Gessi S (2015) A2A and A2B adenosine receptors affect HIF-1α signaling in activated primary microglial cells. Glia 63:1933–1952
Merkel LA, Rivera LM, Colussi DJ, Perrone MH, Smits GJ, Cox BF (1993) In vitro and in vivo characterization of an A1 selective adenosine agonist, RG14202. J Pharmacol Exp Ther 265:699–706
Meyer PT, Bier D, Holschbach MH, Boy C, Olsson RA, Coenen HH, Zilles K, Bauer A (2004) Quantification of cerebral A1 adenosine receptors in humans using [18F]CPFPX and PET. J Cereb Blood Flow Metab 24:323–333
Millan MJ (2003) The neurobiology and control of anxious states. Prog Neurobiol 70:83–244
Montero MF, Saurim R, Bonservizi WG, Koike MK, Taha MO (2014) Heart injury following intestinal ischemia reperfusion in rats is attenuated by association of ischemic preconditioning and adenosine. Acta Cir Bras 29:67–71
Morrison RR, Teng B, Oldenburg PJ, Katwa LC, Schnermann JB, Mustafa SJ (2006) Effects of targeted deletion of A1 adenosine receptors on postischemic cardiac function and expression of adenosine receptor subtypes. Am J Physiol Heart Circ Physiol 291:H1875–H1882
Mostofsky E, Schlaug G, Mukamal KJ, Rosamond WD, Mittleman MA (2010) Coffee and acute ischemic stroke onset: the stroke onset study. Neurology 75:1583–1588
Müller CE (2001) A1 adenosine receptors and their ligands: overview and recent developments. Farmaco 56:77–80
Müller CE, Jacobson KA (2011) Recent developments in adenosine receptor ligands and their potential as novel drugs. Biochim Biophys Acta 1808:1290–1308
Müller CE, Geis U, Grahner B, Lanzner W, Eger K (1996) Chiral pyrrolo[2,3-d]pyrimidine and pyrimido[4,5-b]indole derivatives: structure-activity relationships of potent, highly stereoselective A1 adenosine receptor antagonists. J Med Chem 39:2482–2491
Murthy KS, McHenry L, Grider JR, Makhlouf GM (1995) Adenosine A1 and A2B receptors coupled to distinct interactive signaling pathways in intestinal muscle cells. J Pharmacol Exp Ther 274:300–306
Murthy KS, Grider JR, Makhlouf GM (2000) Heterologous desensitization of response mediated by selective PKC-dependent phosphorylation of G(i-1) and G(i-2). Am J Cell Physiol 279:C925–C934
Musser B, Morgan ME, Leid M, Murray TF, Linden J, Vestal RE (1993) Species comparison of adenosine and β-adrenoceptors in mammalian atrial and ventricular myocardium. Eur J Pharmacol 246:105–111
Mustafa SJ, Morrison RR, Teng B, Pelleg A (2009) Adenosine receptors and the heart: role in regulation of coronary blood flow and cardiac electrophysiology. Handb Exp Pharmacol 193:161–188
Muzzi M, Coppi E, Pugliese AM, Chiarugi A (2013) Anticonvulsant effect of AMP by direct activation of adenosine A1 receptor. Exp Neurol 250:189–193
Nadeem A, Obiefuna PC, Wilson CN, Mustafa SJ (2006) Adenosine A1 receptor antagonist versus montelukast on airway reactivity and inflammation. Eur J Pharmacol 551:116–124
Nakata H, Yoshioka K, Kamiya T, Tsuga H, Oyanagi K (2005) Functions of heteromeric association between adenosine and P2Y receptors. J Mol Neurosci 26:233–238
Nalli AD, Kumar DP, Al-Shboul O, Mahavadi S, Kuemmerle JF, Grider JR, Murthy KS (2014) Regulation of Gβγi-dependent PLC-β3 activity in smooth muscle: inhibitory phosphorylation of PLC-β3 by PKA and PKG and stimulatory phosphorylation of Gαi-GTPase-activating protein RGS2 by PKG. Cell Biochem Biophys 70:867–880
Narlawar R, Lane JR, Doddareddy M, Lin J, Brussee J, Ijzerman AP (2010) Hybrid ortho/allosteric ligands for the adenosine A1 receptor. J Med Chem 53:3028–3037
Nayeem MA, Mustafa SJ (2002) Protein kinase C isoforms and A1 adenosine receptors in porcine coronary smooth muscle cells. Vasc Pharmacol 39:47–54
Neely C (1995) Prevention and treatment of ischemia-reperfusion and endotoxin-related injury using adenosine and purino receptor antagonists. WO patent 1995026728, 12 oct 1995
Nell PG, Albrecht-Küpper B (2009) The adenosine A1 receptor and its ligands. Prog Med Chem 47:163–195
Németh ZH, Bleich D, Csóka B, Pacher P, Mabley JG, Himer L, Vizi ES, Deitch EA, Szabó C, Cronstein BN, Haskó G (2007) Adenosine receptor activation ameliorates type 1 diabetes. FASEB J 21:2379–2388
Newman GC, Hospod FE, Trowbridge SD, Motwani S, Liu Y (1998) Restoring adenine nucleotides in a brain slice model of cerebral reperfusion. J Cereb Blood Flow Metab 18:675–685
Nguyen AT, Baltos JA, Thomas T, Nguyen TD, Muñoz LL, Gregory KJ, White PJ, Sexton PM, Christopoulos A, May LT (2016) Extracellular loop 2 of the adenosine A1 receptor has a key role in orthosteric ligand affinity and agonist efficacy. Mol Pharmacol 90:703–714
Nyce JW, Metzger WJ (1997) DNA antisense therapy for asthma in an animal model. Nature 385:721–725
Obiefuna PC, Batra VK, Nadeem A, Borron P, Wilson CN, Mustafa SJ (2005) A novel A1 adenosine receptor antagonist, L-97-1 [3-[2-(4-aminophenyl)-ethyl]-8-benzyl-7-{2-ethyl-(2-hydroxy-ethyl)-amino]-ethyl}-1-propyl-3,7-dihydro-purine-2,6-dione], reduces allergic responses to house dust mite in an allergic rabbit model of asthma. J Pharmacol Exp Ther 315:329–336
Odagaki Y, Kinoshita M, Ota T, Meana JJ, Callado LF, García-Sevilla JA (2015) Adenosine A1 receptors are selectively coupled to Gα(i-3) in postmortem human brain cortex: Guanosine-5′-O-(3-[(35)S]thio)triphosphate ([(35)S]GTPγS) binding/immunoprecipitation study. Eur J Pharmacol 764:592–598
Olah ME, Stiles GL (2000) The role of receptor structure in determining adenosine receptor activity. Pharmacol Ther 85:55–75
Olah ME, Ren H, Stiles GL (1995) Adenosine receptors: protein and gene structure. Arch Int Pharmacodyn Ther 329(1):135–150
Osswald H, Schnermann J (2011) Methylxanthines and the kidney. Handb Exp Pharmacol 200:391–412
Otsuki L, Dittrich HC, Widder KJ, Blantz R, Thomson S (2005) Method of treatment of disease using an adenosine A1 receptor antagonist. WO patent 200515083, 10 nov 2005
Palacios N, Gao X, McCullough ML, Schwarzschild MA, Shah R, Gapstur S, Ascherio A (2012) Caffeine and risk of Parkinson’s disease in a large cohort of men and women. Mov Disord 27:1276–1282
Pang PS, Mehra M, Maggioni AP, Filippatos G, Middlebrooks J, Turlapaty P, Kazei D, Gheorghiade M (2011) Rationale, design, and results from RENO-DEFEND 1: a randomized, dose-finding study of the selective A1 adenosine antagonist SLV320 in patients hospitalized with acute heart failure. Am Heart J 161:1012–1023
Pankevych H, Korkhov V, Freissmuth M, Nanoff C (2003) Truncation of the A1 adenosine receptor reveals distinct roles of the membrane-proximal carboxyl terminus in receptor folding and G protein coupling. J Biol Chem 278:30283–30293
Panther E, Idzko M, Herouy Y, Rheinen H, Gebicke-Haerter PJ, Mrowietz U, Dichmann S, Norgauer J (2001) Expression and function of adenosine receptors in human dendritic cells. FASEB J 15:1963–1970
Partridge JJ, Wilson CN (2005) A1 adenosine receptor antagonists. WO patent 2005009343, 3 feb 2005
Peart J, Headrick JP (2000) Intrinsic A1 adenosine receptor activation during ischemia or reperfusion improves recovery in mouse hearts. Am J Physiol Heart Circ Physiol 279:H2166–H2175
Peart JN, Headrick JP (2007) Adenosinergic cardioprotection: multiple receptors, multiple pathways. Pharmacol Ther 114:208–221
Peart JN, Headrick JP (2009) Clinical cardioprotection and the value of conditioning responses. Am J Physiol Heart Circ Physiol 296:H1705–H1720
Peeters MC, Wisse LE, Dinaj A, Vroling B, Vriend G, Ijzerman AP (2012) The role of the second and third extracellular loops of the adenosine A1 receptor in activation and allosteric modulation. Biochem Pharmacol 84:76–87
Perígolo-Vicente R, Ritt K, Gonçalves-de-Albuquerque CF, Castro-Faria-Neto HC, Paes-de-Carvalho R, Giestal-de-Araujo E (2014) IL-6, A1 and A2AARs: a crosstalk that modulates BDNF and induces neuroprotection. Biochem Biophys Res Commun 449:477–482
Perlini S, Arosio B, Parmeggiani L, Santambrogio D, Palladini G, Tozzi R, Gatti C, Annoni G, Meyer TE, Ferrari AU (2007) Adenosine A1 receptor expression during the transition from compensated pressure overload hypertrophy to heart failure. J Hypertens 25:449–454
Prediger RD, Batista LC, Takahashi RN (2004) Adenosine A1 receptors modulate the anxiolytic-like effect of ethanol in the elevated plus-maze in mice. Eur J Pharmacol 499:147–154
Prediger RD, da Silva GE, Batista LC, Bittencourt AL, Takahashi RN (2006) Activation of adenosine A1 receptors reduces anxiety-like behavior during acute ethanol withdrawal (hangover) in mice. Neuropsychopharmacology 31:2210–2220
Preti D, Baraldi PG, Moorman AR, Borea PA, Varani K (2015) History and perspectives of A2A adenosine receptor antagonists as potential therapeutic agents. Med Res Rev 35:790–848
Puhl SL, Kazakov A, Müller A, Fries P, Wagner DR, Böhm M, Maack C, Devaux Y (2016) Adenosine A1 receptor activation attenuates cardiac hypertrophy and fibrosis in response to α1 -adrenoceptor stimulation in vivo. Br J Pharmacol 173:88–102
Quitterer U, Lohse MJ (1999) Crosstalk between Galpha(i)- and Galpha(q)-coupled receptors is mediated by Gbetagamma exchange. Proc Natl Acad Sci U S A 96:10626–10631
Randhawa PK, Jaggi AS (2016) Unraveling the role of adenosine in remote ischemic preconditioning-induced cardioprotection. Life Sci 155:140–146
Rebola N, Porciúncula LO, Lopes LV, Oliveira CR, Soares-da-Silva P, Cunha RA (2005) Long-term effect of convulsive behavior on the density of adenosine A1 and A2A receptors in the rat cerebral cortex. Epilepsia 46:159–165
Rieg T, Steigele H, Schnermann J, Richter K, Osswald H, Vallon V (2005) Requirement of intact adenosine A1 receptors for the diuretic and natriuretic action of the methylxanthines theophylline and caffeine. J Pharmacol Exp Ther 313:403–409
Riesenhuber A, Boehm M, Posch M, Aufricht C (2006) Diuretic potential of energy drinks. Amino Acids 31:81–83
Rittiner JE, Korboukh I, Hull-Ryde EA, Jin J, Janzen WP, Frye SV, Zylka MJ (2012) AMP is an adenosine A1 receptor agonist. J Biol Chem 287:5301–5309
Rivera-Oliver M, Díaz-Ríos M (2014) Using caffeine and other adenosine receptor antagonists and agonists as therapeutic tools against neurodegenerative diseases: a review. Life Sci 101:1–9
Rivkees SA, Wendler CC (2012) Regulation of cardiovascular development by adenosine and adenosine-mediated embryo protection. Arterioscler Thromb Vasc Biol 32:851–855
Romagnoli R, Baraldi PG, Moorman AR, Iaconinoto MA, Carrion MD, Cara CL, Tabrizi MA, Preti D, Fruttarolo F, Baker SP, Varani K, Borea PA (2006) Microwave-assisted synthesis of thieno[2,3-c]pyridine derivatives as a new series of allosteric enhancers at the adenosine A1 receptor. Bioorg Med Chem Lett 16:5530–5533
Romagnoli R, Baraldi PG, Carrion MD, Cara CL, Cruz-Lopez O, Iaconinoto MA, Preti D, Shryock JC, Moorman AR, Vincenzi F, Varani K, Borea PA (2008) Synthesis and biological evaluation of 2-amino-3-(4-chlorobenzoyl)-4-[N-(substituted) piperazin-1-yl]thiophenes as potent allosteric enhancers of the A1 adenosine receptor. J Med Chem 51:5875–5879
Romagnoli R, Baraldi PG, Tabrizi MA, Gessi S, Borea PA, Merighi S (2010) Allosteric enhancers of A1 adenosine receptors: state of the art and new horizons for drug development. Curr Med Chem 17:3488–3502
Romagnoli R, Baraldi PG, Carrion MD, Cara CL, Cruz-Lopez O, Salvador MK, Preti D, Tabrizi MA, Moorman AR, Vincenzi F, Borea PA, Varani K (2012a) Synthesis and biological evaluation of 2-amino-3-(4-chlorobenzoyl)-4-[(4-arylpiperazin-1-yl)methyl]-5-substituted-thiophenes. Effect of the 5-modification on allosteric enhancer activity at the A1 adenosine receptor. J Med Chem 55:7719–7735
Romagnoli R, Baraldi PG, Carrion MD, Cara CL, Cruz-Lopez O, Salvador MK, Preti D, Tabrizi MA, Shryock JC, Moorman AR, Vincenzi F, Varani K, Borea PA (2012b) Structure-activity relationships of 2-amino-3-aroyl-4-[(4-arylpiperazin-1-yl)methyl]thiophenes. Part 2: Probing the influence of diverse substituents at the phenyl of the arylpiperazine moiety on allosteric enhancer activity at the A1 adenosine receptor. Bioorg Med Chem 20:996–1007
Romagnoli R, Baraldi PG, Carrion MD, Lopez Cara C, Kimatrai Salvador M, Preti D, Aghazadeh Tabrizi M, Moorman AR, Vincenzi F, Borea PA, Varani K (2013) Synthesis and biological effects of novel 2-amino-3-(4-chlorobenzoyl)-4-substituted thiophenes as allosteric enhancers of the A1 adenosine receptor. Eur J Med Chem 67:409–427
Romagnoli R, Baraldi PG, Carrion MD, Cruz-Lopez O, Cara CL, Saponaro G, Preti D, Tabrizi MA, Baraldi S, Moorman AR, Vincenzi F, Borea PA, Varani K (2014a) Synthesis and biological evaluation of novel 2-amino-3-aroyl-4-neopentyl-5-substituted thiophene derivatives as allosteric enhancers of the A1 adenosine receptor. Bioorg Med Chem 22:148–166
Romagnoli R, Baraldi PG, IJzerman AP, Massink A, Cruz-Lopez O, Lopez-Cara LC, Saponaro G, Preti D, Aghazadeh Tabrizi M, Baraldi S, Moorman AR, Vincenzi F, Borea PA, Varani K (2014b) Synthesis and biological evaluation of novel allosteric enhancers of the A1 adenosine receptor based on 2-amino-3-(4′-chlorobenzoyl)-4-substituted-5-arylethynyl thiophene. J Med Chem 57(18):7673–7686
Romagnoli R, Baraldi PG, Moorman AR, Borea PA, Varani K (2015) Current status of A1 adenosine receptor allosteric enhancers. Future Med Chem 7:1247–1259
Roman V, Keijser JN, Luiten PG, Meerlo P (2008) Repetitive stimulation of adenosine A1 receptors in vivo: changes in receptor numbers, G-proteins and A1 receptor agonist-induced hypothermia. Brain Res 1191:69–74
Ross GW, Abbott RD, Petrovitch H, Morens DM, Grandinetti A, Tung KH, Tanner CM, Masaki KH, Blanchette PL, Curb JD, Popper JS, White LR (2000) Association of coffee and caffeine intake with the risk of Parkinson disease. JAMA 283:2674–2679
Rudolphi KA, Schubert P (1997) Modulation of neuronal and glial cell function by adenosine and neuroprotection in vascular dementia. Behav Brain Res 83:123–128
Ruiz MÁ, León DA, Albasanz JL, Martín M (2011) Desensitization of adenosine A1 receptors in rat immature cortical neurons. Eur J Pharmacol 670:365–371
Sabbah HN, Gupta RC, Kohli S, Wang M, Rastogi S, Zhang K, Zimmermann K, Diedrichs N, Albrecht-Küpper BE (2013) Chronic therapy with a partial adenosine A1 receptor agonist improves left ventricular function and remodeling in dogs with advanced heart failure. Circ Heart Fail 6:563–571
Sachdeva S, Gupta M (2013) Adenosine and its receptors as therapeutic targets: an overview. Saudi Pharm J 21:245–253
Sadigh-Lindell B, Sylvén C, Berglund M, Eriksson BE (2003) Role of adenosine and opioid-receptor mechanisms for pain in patients with silent myocardial ischemia or angina pectoris: a double-blind, placebo-controlled study. J Cardiovasc Pharmacol 42:757–763
Salazar-Martinez E, Willett WC, Ascherio A, Manson JE, Leitzmann MF, Stampfer MJ, Hu FB (2004) Coffee consumption and risk for type 2 diabetes mellitus. Ann Intern Med 140:1–8
Salvatore CA, Jacobson MA, Taylor HE, Linden J, Johnson RG (1993) Molecular cloning and characterization of the human A3 adenosine receptor. Proc Natl Acad Sci U S A 90:10365–10369
Santiago FE, Fior-Chadi DR, Carrettiero DC (2015) Alpha2-adrenoceptor and adenosine A1 receptor within the nucleus tractus solitarii in hypertension development. Auton Neurosci 187:36–44
Sawynok J (2016) Adenosine receptor targets for pain. Neuroscience 338:1–18
Sawynok J, Reid AR (2012) Caffeine inhibits antinociception by acetaminophen in the formalin test by inhibiting spinal adenosine A1 receptors. Eur J Pharmacol 674:248–254
Scheiff AB, Yerande SG, El-Tayeb A, Li W, Inamdar GS, Vasu KK, Sudarsanam V, Müller CE (2010) 2-amino-5-benzoyl-4-phenylthiazoles: development of potent and selective adenosine A1 receptor antagonists. Bioorg Med Chem 18:2195–2203
Schenone S, Brullo C, Musumeci F, Bruno O, Botta M (2010) A1 receptors ligands: past, present and future trends. Curr Top Med Chem 10:878–901
Schepp CP, Reutershan J (2008) Bench-to-bedside review: adenosine receptors--promising targets in acute lung injury? Crit Care 12(5):226
Schnurr M, Toy T, Shin A, Hartmann G, Rothenfusser S, Soellner J, Davis ID, Cebon J, Maraskovsky E (2004) Role of adenosine receptors in regulating chemotaxis and cytokine production of plasmacytoid dendritic cells. Blood 103:1391–1397
Schoelch C, Kuhlmann J, Gossel M, Mueller G, Neumann-Haefelin C, Belz U, Kalisch J, Biemer-Daub G, Kramer W, Juretschke HP, Herling AW (2004) Characterization of adenosine A1 receptor-mediated antilipolysis in rats by tissue microdialysis, 1H-spectroscopy, and glucose clamp studies. Diabetes 53:1920–1926
Scholl DJ, Wells JN (2000) Serine and alanine mutagenesis of the nine native cysteine residues of the human A1 adenosine receptor. Biochem Pharmacol 60:1647–1654
Schulte G, Fredholm BB (2002a) Diverse inhibitors of intracellular signalling act as adenosine receptor antagonists. Cell Signal 14:109–113
Schulte G, Fredholm BB (2002b) Signaling pathway from the human adenosine A3 receptor expressed in Chinese hamster ovary cells to the extracellular signal-regulated kinase 1/2. Mol Pharmacol 62:1137–1146
Serchov T, Clement HW, Schwarz MK, Iasevoli F, Tosh DK, Idzko M, Jacobson KA, de Bartolomeis A, Normann C, Biber K, van Calker D (2015) Increased signaling via adenosine A1 receptors, sleep deprivation, imipramine, and ketamine inhibit depressive-like behavior via induction of Homer1a. Neuron 87:549–562
Shearer J, Severson DL, Su L, Belardinelli L, Dhalla AK (2009) Partial A1 adenosine receptor agonist regulates cardiac substrate utilization in insulin-resistant rats in vivo. J Pharmacol Exp Ther 328:306–311
Shen J, Halenda SP, Sturek M, Wilden PA (2005) Cell-signaling evidence for adenosine stimulation of coronary smooth muscle proliferation via the A1 adenosine receptor. Circ Res 97:574–582
Shirley DG, Walter SJ, Noormohamed FH (2002) Natriuretic effect of caffeine: assessment of segmental sodium reabsorption in humans. Clin Sci (Lond) 103:461–466
Shryock JC, Travagli HC, Belardinelli L (1992) Evaluation of N-0861, (+−)-N6-endonorbornan-2-yl-9-methyladenine, as an A1 subtype-selective adenosine receptor antagonist in the guinea pig isolated heart. J Pharmacol Exp Ther 260:1292–1299
Snowdy S, Liang HX, Blackburn B, Lum R, Nelson M, Wang L, Pfister J, Sharma BP, Wolff A, Belardinelli L (1999) A comparison of an A1 adenosine receptor agonist (CVT-510) with diltiazem for slowing of AV nodal conduction in guinea-pig. Br J Pharmacol 126:137–146
Sodhi P, Hartwick AT (2014) Adenosine modulates light responses of rat retinal ganglion cell photoreceptors througha cAMP-mediated pathway. J Physiol 592:4201–4220
Spicuzza L, Di Maria G, Polosa R (2006) Adenosine in the airways: implications and applications. Eur J Pharmacol 533:77–88
Srinivas M, Shryock JC, Dennis DM, Baker SP, Belardinelli L (1997) Differential A1 adenosine receptor reserve for two actions of adenosine on guinea pig atrial myocytes. Mol Pharmacol 52:683–691
Staehr PM, Dhalla AK, Zack J, Wang X, Ho YL, Bingham J, Belardinelli L (2013) Reduction of free fatty acids, safety, and pharmacokinetics of oral GS-9667, an A1 adenosine receptor partial agonist. J Clin Pharmacol 53:385–392
Stone TW, Ceruti S, Abbracchio MP (2009) Adenosine receptors and neurological disease: neuroprotection and neurodegeneration. Handb Exp Pharmacol 193:535–587
Sun X, Barnes S, Baldridge WH (2002) Adenosine inhibits calcium channel currents via A1 receptors on salamander retinal ganglion cells in a mini-slice preparation. J Neurochem 81:550–556
Sun CX, Young HW, Molina JG, Volmer JB, Schnermann J, Blackburn MR (2005) A protective role for the A1 adenosine receptor in adenosine-dependent pulmonary injury. J Clin Invest 115:35–43
Sundarama U, Hassanainb H, Suntresc Z, Yud JG, Cookee HJ, Guzmand J, Christofid FL (2003) Rabbit chronic ileitis leads to up-regulation of adenosine A1/A3 gene products, oxidative stress, and immune modulation. Biochem Pharmacol 65:1529–1538
Svenningsson P, Hall H, Sedvall G, Fredholm BB (1997) Distribution of adenosine receptors in the postmortem human brain: an extended autoradiographic study. Synapse 27:322–335
Świąder MJ, Kotowski J, Łuszczki JJ (2014) Modulation of adenosinergic system and its application for the treatment of epilepsy. Pharmacol Rep 66:335–342
Szkudelski T, Szkudelska K (2015) Regulatory role of adenosine in insulin secretion from pancreatic β-cells--action via adenosine A1 receptor and beyond. J Physiol Biochem 71:133–140
Tang Z, Diamond MA, Chen JM, Holly TA, Bonow RO, Dasgupta A, Hyslop T, Purzycki A, Wagner J, McNamara DM, Kukulski T, Wos S, Velazquez EJ, Ardlie K, Feldman AM (2007) Polymorphisms in adenosine receptor genes are associated with infarct size in patients with ischemic cardiomyopathy. Clin Pharmacol Ther 82:435–440
Tanner GA, Tanner JA (2001) Chronic caffeine consumption exacerbates hypertension in rats with polycystic kidney disease. Am J Kidney Dis 38:1089–1095
Tateyama M, Kubo Y (2016) Stabilizing effects of G protein on the active conformation of adenosine A1 receptor differ depending on G protein type. Eur J Pharmacol 788:122–131
Tendera M, Gaszewska-Żurek E, Parma Z, Ponikowski P, Jankowska E, Kawecka-Jaszcz K, Czarnecka D, Krzemińska-Pakuła M, Bednarkiewicz Z, Sosnowski M, Ochan Kilama M, Agrawal R (2012) The new oral adenosine A1 receptor agonist capadenoson in male patients with stable angina. Clin Res Cardiol 101:585–591
Thompson GW, Horackova M, Armour JA (2002) Role of P1 purinergic receptors in myocardial ischemia sensory transduction. Cardiovasc Res 53:888–901
Tofovic SP, Kost CK Jr, Jackson EK, Bastacky SI (2002) Long-term caffeine consumption exacerbates renal failure in obese, diabetic, ZSF1 (fa-fa(cp)) rats. Kidney Int 61:1433–1444
Tofovic SP, Salah EM, Jackson EK, Melhem M (2007) Early renal injury induced by caffeine consumption in obese, diabetic ZSF1 rats. Ren Fail 29:891–902
Tomé AR, Feng D, Freitas RM (2010) The effects of alpha-tocopherol on hippocampal oxidative stress prior to in pilocarpine-induced seizures. Neurochem Res 35:580–587
Tranberg CE, Zickgraf A, Giunta BN, Luetjens H, Figler H, Murphree LJ, Falke R, Fleischer H, Linden J, Scammells PJ, Olsson RA (2002) 2-amino-3-aroyl-4,5-alkylthiophenes: agonist allosteric enhancers at human A1 adenosine receptors. Med Chem 45:382–389
Tupone D, Cetas JS, Morrison SF (2016) Hibernation, hypothermia and a possible therapeutic "shifted homeostasis" induced by central activation of A1 adenosine receptor (A1AR). Jpn J Psychopharmacol 36:51–54
Vallon V, Osswald H (2009) Adenosine receptors and the kidney. Handb Exp Pharmacol 193:443–470
Vallon V, Miracle C, Thomson S (2008) Adenosine and kidney function: potential implications in patients with heart failure. Eur J Heart Fail 10:176–187
van Dam RM, Hu FB (2005) Coffee consumption and risk of type 2 diabetes: a systematic review. JAMA 294:97–104
van der Klein PA, Kourounakis AP, IJzerman AP (1999) Allosteric modulation of the adenosine A1 receptor. Synthesis and biological evaluation of novel 2-amino-3-benzoylthiophenes as allosteric enhancers of agonist binding. J Med Chem 42:3629–3635
van Galen PJ, van Bergen AH, Gallo-Rodriguez C, Melman N, Olah ME, IJzerman AP, Stiles GL, Jacobson KA (1994) A binding site model and structure-activity relationships for the rat A3 adenosine receptor. Mol Pharmacol 45:1101–1111
van Tilburg EW, van der Klein PA, de Groote M, Beukers MW, IJzerman AP (2001) Substituted 4-phenyl-2-(phenylcarboxamido)-1,3-thiazole derivatives as antagonists for the adenosine A1 receptor. Bioorg Med Chem Lett 11:2017–2019
van Veldhoven JP, Chang LC, von Frijtag Drabbe Künzel JK, Mulder-Krieger T, Struensee-Link R, Beukers MW, Brussee J, IJzerman AP (2008) A new generation of adenosine receptor antagonists: from di- to trisubstituted aminopyrimidines. Bioorg Med Chem 16:2741–2752
Vincenzi F, Targa M, Romagnoli R, Merighi S, Gessi S, Baraldi PG, Borea PA, Varani K (2014) TRR469, a potent A1 adenosine receptor allosteric modulator, exhibits anti-nociceptive properties in acute and neuropathic pain models in mice. Neuropharmacology 81:6–14
Vincenzi F, Ravani A, Pasquini S, Merighi S, Gessi S, Romagnoli R, Baraldi PG, Borea PA, Varani K (2016) Positive allosteric modulation of A1 adenosine receptors as a novel and promising therapeutic strategy for anxiety. Neuropharmacology 111:283–292
Vizi E, Huszár E, Csoma Z, Böszörményi-Nagy G, Barát E, Horváth I, Herjavecz I, Kollai M (2002) Plasma adenosine concentration increases during exercise: a possible contributing factor in exercise-induced bronchoconstriction in asthma. J Allergy Clin Immunol 109:446–448
Von Lubitz DK, Lin RC, Melman N, Ji XD, Carter MF, Jacobson KA (1994) Chronic administration of selective adenosine A1 receptor agonist or antagonist in cerebral ischemia. Eur J Pharmacol 256:161–167
Von Lubitz DK, Lin RC, Jacobson KA (1995) Cerebral ischemia in gerbils: effects of acute and chronic treatment with adenosine A2A receptor agonist and antagonist. Eur J Pharmacol 287:295–302
Vyas FS, Hargreaves AJ, Bonner PL, Boocock DJ, Coveney C, Dickenson JM (2016) A1 adenosine receptor-induced phosphorylation and modulation of transglutaminase 2 activity in H9c2 cells: a role in cell survival. Biochem Pharmacol 107:41–58
Wan WJ, Cui DM, Yang X, Hu JM, Li CX, Hu SL, Trier K, Zeng JW (2011) Expression of adenosine receptors in human retinal pigment epithelium cells in vitro. Chin Med J 124:1139–1144
Wardas J (2002) Neuroprotective role of adenosine in the CNS. Pol J Pharmacol 54:313–326
Weaver DR, Reppert SM (1992) Adenosine receptor gene expression in rat kidney. Am J Physio 263:F991–F995
Welch WJ (2015) Adenosine, type 1 receptors: role in proximal tubule Na+ reabsorption. Acta Physiol (Oxf) 213:242–248
Wider KJ, Dittrich H, Thomson S, Blantz R (2004) Method of improved diuresis in individuals with impaired renal function WO patent 2004096228, 11 nov 2004
Wilson CN (2006) Methods and pharmaceutical compositions for treating sepsis. US patent 20060276378, 27 apr 2006
Wilson CN, Batra VK (2002) Lipopolysaccharide binds to and activates A1 adenosine receptors on human pulmonary artery endothelial cells. J Endotoxin Res 8:263–271
Wilson CN, Partridge JJ (2007) Compositions and methods for treating respiratory disorders. US patent 20070219223, 27 apr 2007
Wood JD (2004) Enteric neuroimmunophysiology and pathophysiology. Gastroenterology 127:635–657
Wu WP, Hao JX, Halldner L, Lövdahl C, DeLander GE, Wiesenfeld-Hallin Z, Fredholm BB, Xu XJ (2005) Increased nociceptive response in mice lacking the adenosine A1 receptor. Pain 113:395–404
Xi L, Das A, Zhao ZQ, Merino VF, Bader M, Kukreja RC (2008) Loss of myocardial ischemic postconditioning in adenosine A1 and bradykinin B2 receptors gene knockout mice. Circulation 118:S32–S37
Yamaguchi D, Terayama R, Omura S, Tsuchiya H, Sato T, Ichikawa H, Sugimoto T (2014) Effect of adenosine A1 receptor agonist on the enhanced excitability of spinal dorsal horn neurons after peripheral nerve injury. Int J Neurosci 124:213–222
Yang GK, Fredholm BB, Kieffer TJ, Kwok YN (2012) Improved blood glucose disposal and altered insulin secretion patterns in adenosine A1 receptor knockout mice. Am J Physiol Endocrinol Metab 303:E180–E190
Yang T, Gao X, Sandberg M, Zollbrecht C, Zhang XM, Hezel M, Liu M, Peleli M, Lai EY, Harris RA, Persson AE, Fredholm BB, Jansson L, Carlström M (2015) Abrogation of adenosine A1 receptor signalling improves metabolic regulation in mice by modulating oxidative stress and inflammatory responses. Diabetologia 58:1610–1620
Yavuz T, Bertolet B, Bebooul Y, Tunerir B, Aslan R, Ocal A, Ybribim E, Kutsal A (2004) Role of endogenous adenosine in atrial fibrillation after coronary artery bypass graft. Clin Cardiol 27:343–346
Yip L, Fathman CG (2014) Type 1 diabetes in mice and men: gene expression profiling to investigate disease pathogenesis. Immunol Res 58:340–350
Yip L, Taylor C, Whiting CC, Fathman CG (2013) Diminished adenosine A1 receptor expression in pancreatic α-cells may contribute to the pathology of type 1 diabetes. Diabetes 62:4208–4219
Yoshioka K, Hosoda R, Kuroda Y, Nakata H (2002) Hetero-oligomerization of adenosine A1 receptors with P2Y1 receptors in rat brains. FEBS Lett 531:299–303
Zahler S, Becker BF, Raschke P, Gerlach E (1994) Stimulation of endothelial adenosine A1 receptors enhances adhesion of neutrophils in the intact guinea pig coronary system. Cardiovasc Res 28:1366–1372
Zeron MM, Hansson O, Chen N, Wellington CL, Leavitt BR, Brundin P, Hayden MR, Raymond LA (2002) Increased sensitivity to N-methyl-D-aspartate receptor-mediated excitotoxicity in a mouse model of Huntington’s disease. Neuron 33:849–860
Zhang J, Belardinelli L, Jacobson KA, Otero DH, Baker SP (1997) Persistent activation by and receptor reserve for an irreversible A1-adenosine receptor agonist in DDT1 MF-2 cells and in guinea pig heart. Mol Pharmacol 52:491–498
Zhang M, Budak MT, Lu W, Khurana TS, Zhang X, Laties AM, Mitchell CH (2006) Identification of the A3 adenosine receptor in rat retinal ganglion cells. Mol Vis 12:937–944
Zhang S, Li H, Li B, Zhong D, Gu X, Tang L, Wang Y, Wang C, Zhou R, Li Y, He Y, Chen M, Huo Y, Liu XL, Chen JF (2015) Adenosine A1 receptors selectively modulate oxygen-induced retinopathy at the Hyperoxic and hypoxic phases by distinct cellular mechanisms. Invest Ophthalmol Vis Sci 56:8108–8119
Zhong Y, Yang Z, Huang WC, Luo X (2013) Adenosine, adenosine receptors and glaucoma: an updated overview. Biochim Biophys Acta 1830:2882–2890
Zizzo MG, Mulè F, Serio R (2006) Inhibitory responses to exogenous adenosine in murine proximal and distal colon. Br J Pharmacol 148:956–963
Zuccato C, Cattaneo E (2014) Huntington’s disease. Handb Exp Pharmacol 220:357–409
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Varani, K., Vincenzi, F., Merighi, S., Gessi, S., Borea, P.A. (2017). Biochemical and Pharmacological Role of A1 Adenosine Receptors and Their Modulation as Novel Therapeutic Strategy. In: Atassi, M. (eds) Protein Reviews. Advances in Experimental Medicine and Biology(), vol 1051. Springer, Singapore. https://doi.org/10.1007/5584_2017_61
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