Possible therapeutic benefits of adenosine-potentiating drugs in reducing age-related degenerative disease in dogs and cats

Journal of Veterinary Pharmacology and Therapeutics

Volumn 26, Issue 5, 2003, Pages 327-335

  Scaramuzzi, R J ^a   Baker, D J ^b,c  

^a ROYAL VETERINARY COLLEGE   (United Kingdom)

^b Intervet UK   (United Kingdom)

^c Walnut Farm   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

2 [4 (2 CARBOXYETHYL)PHENETHYLAMINO]ADENOSINE 5' (N ETHYLCARBOXAMIDE); 2 ANILINOADENOSINE; 6 N (2 HYDROXYCYCLOPENTYL)ADENOSINE; 6 N (3 IODOBENZYL)ADENOSINE 5' N METHYLCARBOXAMIDE; 6 N CYCLOPENTYLADENOSINE; 8 CYCLOPENTYL 1,3 DIPROPYLXANTHINE; 8 PHENYLTHEOPHYLLINE; 9 CHLORO 2 (2 FURYL) 5,6 DIHYDRO 5 IMINO 1,2,4 TRIAZOLO[2,3 C]QUINAZOLINE; ADENOSINE; ADENOSINE 5' (N ETHYLCARBOXAMIDE); ADENOSINE RECEPTOR; ADENOSINE RECEPTOR BLOCKING AGENT; ADENOSINE RECEPTOR STIMULATING AGENT; DOPAMINE; GLUTAMIC ACID; METRIFUDIL; PHENYLISOPROPYLADENOSINE; PHOSPHODIESTERASE; PROPENTOFYLLINE;

AGING; ALZHEIMER DISEASE; CARDIOVASCULAR EFFECT; CASTRATION; CAT DISEASE; CENTRAL NERVOUS SYSTEM; CEREBROVASCULAR ACCIDENT; CONGESTIVE HEART FAILURE; DEGENERATIVE DISEASE; DOG DISEASE; DRUG EFFECT; DRUG MECHANISM; ENZYME INHIBITION; ERYTHROCYTE; GENITAL SYSTEM; GONADECTOMY; HUMAN; IMMUNE SYSTEM; METABOLISM; NEUROMODULATION; NONHUMAN; PRIORITY JOURNAL; QUALITY OF LIFE; REVIEW; SENILE DEMENTIA; SKELETAL MUSCLE; SUPRAVENTRICULAR TACHYCARDIA; TISSUE PERFUSION; VASCULAR SMOOTH MUSCLE;

ADENOSINE; AGING; ANIMALS; CAT DISEASES; CATS; DOG DISEASES; DOGS; NEURODEGENERATIVE DISEASES; NEUROPROTECTIVE AGENTS;

ANIMALIA; CANIS FAMILIARIS; FELIS CATUS;

EID: 0242468241     PISSN: 01407783     EISSN: None     Source Type: Journal    
DOI: 10.1046/j.1365-2885.2003.00527.x     Document Type: Review

References (140)

1. Auchampach, J.A. & Bolli, R. (1999) Adenosine receptor subtypes in the heart: therapeutic opportunities and challenges. American Journal of Physiology, 276, H1113-H1116
2. Banati, R.B., Schubert, P., Rothe, G., Gehrmann, J., Rudolphi, K., Valet, G. & Kreutzberg, G.W. (1994) Modulation of intracellular formation of reactive oxygen intermediates in peritoneal macrophages and microglia/brain macrophages by propentofylline. Journal of Cerebral Blood Flow and Metabolism, 14, 145-149.
3. Baraldi, P.G., Cacciari, B., Romagnoli, R., Merighi, S., Varani, K., Borea, P.A. & Spalluto, G. (2000) A(3) adenosine receptor ligands: history and perspective. Medicine Research Reviews, 20, 103-128.
4. Bath, P.M., Bath, F.J. & Asplund, K. (2000) Pentoxifylline, propentofylline and pentofylline for acute ischaemic stroke. Cochrane Database of Systematic Reviews, 2, CD000162.
5. Baum, M.S. & Ahern, K. (1986) Adenosine potentiates the effects of LH and isoproterenol on luteal cells but not on isolated corpora lutea. Acta Physiologica Scandinavia, 127, 373-379.
6. Bhat, S.G., Wilson, M. & Ramkumar, V. (1998) Age-dependent reductions in A1 adenosine receptor expression in rat testes. American Journal of Physiology, 274, C1057-C1064.
7. Billig, H., Thelander, H. & Roseberg, S. (1988) Adenosine receptor-mediated effects by nonmetabolizable adenosine analogs in preovulatory rat granulosa cell: a putative local regulatory role of adenosine in the ovary. Endocrinology, 122, 52-61.
8. Billig, H., Rosberg, S., Johanson, C. & Ahren, K. (1989) Adenosine as substrate and receptor agonist in the ovary. Steroids, 54, 523-542.
9. Bush, P. Souness, J.E. & Chagoya de Sanchez, V. (1988) Effect of age and time of day on the adenosine modulation of basal and insulin-stimulated glucose transport in rat adipocytes. International Journal of Biochemistry, 20, 279-283.
10. Chiang, P.H., Wu, S.N., Tsai, E.M., Wu, C.C., Shen, M.R., Huang, C.H. & Chiang, C.P. (1994) Adenosine modulation of neurotransmission in penile erection. British Journal of Clinical Pharmacology, 38, 357-362.
11. Ciaraldi, T.P., Morales, A.J., Hickman, M.G., Odom-Ford, R., Olefsky, J.M. & Yen, S.S.C. (1997) Cellular insulin resistance in adipocytes from obese polycystic ovary syndrome subjects involves adenosine modulation of insulin sensitivity. Journal of Clinical Endocrinology and Metabolism, 82, 1421-1425.
12. Collis, M.G. (1989) The vasodilator role of adenosine. Pharmacological Therapeutics 41, 43-62.
13. Collis, M.G. (1991) Effect of adenosine on the coronary circulation. In Adenosine and Adenine Nucleotides as Regulators of Cellular Function. Ed. Phillis, J.W. pp. 171-180. CRC Press, West Palm Beach, FL.
14. Collis, M.G. & Hourani, S.M. (1993) Adenosine receptor subtypes. Trends in Pharmacological Science, 14, 360-366.
15. Conti, M., Biotin, C., Demanno, D., Migliaccio, S., Monaco, L. & Szymeczek, C. (1989) Characterization and function of adenosine receptors in the testis. Annals of the New York Academy of Science, 564, 39-47.
16. Correia-de-Sa, P., Timoteo, M.A. & Ribeiro, J.A. (2000) A(2A) adenosine receptor facilitation of neuromuscular transmission: influence of stimulus paradigm on calcium mobilization. Journal of Neurochemistry, 74, 2462-2469.
17. Cronstein, B.N. (1994) Adenosine, an endogenous anti-inflammatory agent. Journal of Applied Physiology, 76, 5-13.
18. Cronstein, B.N., Levin, R.I., Philips, M., Hirschhorn, R., Abramson, S.B. & Weissmann, G. (1992) Neutrophil adherence to endothelium is enhanced via adenosine A1 receptors and inhibited via adenosine A2 receptors. Journal of Immunology, 148, 2201-2206.
19. Cronstein, B.N., Naime, D. & Firestein, G. (1995) The anti-inflammatory effects of an adenosine kinase inhibitor are mediated by adenosine. Arthritis and Rheumatism, 38, 1040-1045.
20. Cusack, N.J. & Hourani, M.O. (1991) Adenosine, adenine nucleosides and platelet function. In Adenosine and Adenine Nucleotides as Regulators of Cellular Function. Ed. Phillis, J.W., pp. 121-131. CRC Press, West Palm Beach, FL.
21. Daval, J.L., Nicolas, F. & Doriat, J.F. (1996) Adenosine physiology and pharmacology: how about A2 receptors? Pharmacological Therapeutics, 71, 325-335.
22. Davies, M. (1996) Canine and Feline Geriatrics. In Library of Veterinary Practice. Eds Sutton, J.B. & Swift, S.T. Blackwell Science Ltd. Oxford, UK.
23. Di Sole, F., Cerull, R., Petzke, S., Casavola, V., Burckhardt, G. & Helmle-Kolb, C. (2003) Bimodal acute effects of A(1) adenosine receptor activation on Na(+)/H(+) exchanger 3 in opossum kidney cells. Journal of the American Society for Nephrology, 14, 1720-1730.
24. Dickenson, J.M. & Hill, S.J. (1993) Adenosine A1-receptor stimulated increases in intracellular calcium in the smooth muscle cell line DDT1MF02. British Journal of Pharmacology, 108, 85-92.
25. Dixon, A.K., Gubitz, A.K., Sirinathsinghji, D.J., Richardson, P.J. & Freeman, T.C. (1996) Tissue distribution of adenosine receptor mRNAs in the rat. British Journal of Pharmacology, 118, 1461-1468.
26. Dubey, R.K., Gillespie, D.G., Mi, Z., Roselle, M., Keller, P.J. & Jackson, E.K. (2000) Estradiol inhibits smooth muscle cell growth in part by activating the cAMP-adenosine pathway. Hypertension, 35, 262-266.
27. Ekonomou, A., Pagonopoulou, O. & Angelatou, F. (2000) Age-dependent changes in adenosine A1 receptor and uptake site binding in the mouse brain: an autoradiographic study. Journal of Neuroscience Research, 60, 257-265,
28. 2B receptors. Pharmacological Reviews, 49, 381-402.
29. 2B receptors: a novel therapeutic target in asthma. Trends in Pharmacological Science, 19, 148-153.
30. Ferre, S., Fuse, K., von Euler, G., Johansson, B. & Fredholm, B.B. (1992) Adenosine-dopamine interactions in the brain. Neuroscience, 51, 501-512.
31. Ferre, S., Popoli, P., Gimenez-Llort, L., Finnman, U.B., Martinez, E., Scotti de Carolis, A. & Fuxe, K. (1994) Postsynaptic antagonistic interaction between adenosine A1 and dopamine D1 receptors. Neuroreport, 6, 73-76.
32. Ferre, S., Karcz-Kubicha, M., Hope, B.T., Popoli, P. & Ciruela, F. (2002) Proceedings of the New York Academy of Science, 99, 11940-11945.
33. Filippi, S., Mancini, M., Amerini, S., Bartolini, M., Natali, A., Mancina, R., Forti, G., Ledda, F. & Maggi, M. (2000) Functional adenosine receptors in human corpora carvernosa. International Journal of Andrology, 23, 210-217.
34. Fishman, P. & Bar-Yehuda, S. (2003) Pharmacology and therapeutic applications of A3 receptor subtype. Current Topics in Medicinal Chemistry, 3, 463-469.
35. Fishman, P., Bar-Yehuda, S., Madi L. & Cohn, I. (2002) A3 adenosine receptor as a target for cancer therapy Anticancer. Drugs, 13, 437-443.
36. Ford, G.A., Huffman, B.B., Vestal, R.E. & Blaschke, T.F. (1992) Age-related changes in adenosine and beta-adrenoceptor responsiveness of vascular smooth muscle in man. British Journal of Clinical Pharmacology, 33, 83-87.
37. Fredholm, B.B. & Duner-Engstrom, M. (1989) Propentofylline and a hydroxy metabolite augment A2-receptor mediated cyclic AMP accumulation and attenuate A1-receptor mediated inhibition of acetylcholine release in the rat hippocampus. Pharmacological Toxicology, 65, 347-351.
38. Fredholm, B.B. & Lindgren, E. (1984) The effect of alkylxanthines and other phosphodiesterase inhibitors on adenosine-receptor mediated decrease in lipolysis and cyclic AMP accumulation in rat fat cells. Acta Pharmacologica and Toxicologica (Copenhagen), 54, 64-71.
39. Fredholm, B.B. & Lindstrom, K. (1986) The xanthine derivative 1-(5′-oxohexyl)-3-methyl-7-propyl xanthine (HWA 285) enhances the actions of adenosine. Acta Pharmacologica and Toxicologica (Copenhagen), 58, 187-192.
40. Fredholm, B.B., Fastbom, J., Kvanta, A., Gerwins, P. & Parkinson, F. (1992) Further evidence that propentofylline (HWA 285) influences both adenosine receptors and adenosine transport. Fundamentals of Clinical Pharmacology, 6, 99-111.
41. Fredholm, B.B., Arslan, G., Halldner, L., Kull, B., Schulte, G. & Wasserman, W. (2000) Structure and function of adenosine receptors and their genes. Naunyn-Schmiedeberg's Archives of Pharmacology, 362, 364-374.
42. Fuxe, K., Ferre, S., Zoli, M., Agnati, L.F. (1998) Integrated events in central dopamine transmission as analyzed at multiple levels. Evidence for intramembrane adenosine A2A/dopamine D2 and adenosine A1/ dopamine D1 receptor interactions in the basal ganglia. Brain Research Review, 26, 258-273.
43. Gao, E., Snyder, D.L., Johnson, M.D., Friedman, E., Roberts, J. & Horwitz, J. (1997) The effect of age on adenosine A1 receptor function in the rat heart. Journal of Molecular and Cellular Cardiology, 29, 593-602.
44. Gessi, S., Varani, K., Merighi, S., Ongini, E. & Borea, P.A. (2000) A(2A) adenosine receptors in human peripheral blood cells. British Journal of Pharmacology, 129, 2-11.
45. Gidday, J.M., Fitzgibbons, J.C., Shah, R., Kraujalis, M.J. & Park, T.S. (1995) Reduction in cerebral ischemic injury in the newborn rat by potentiation of endogenous adenosine. Paediatrics Research, 38, 306-311.
46. Harper, E.J., Stack, D.M., Watson, T.D. & Moxham, G. (2001) Effects of feeding regimens on bodyweight, composition and condition score in cats following ovariohysterectomy. Journal of Small Animal Practice, 42, 433-438.
47. Henderson, V.W. (1997) The epidemology of estrogen replacement therapy and Alzheimer's disease. Neurology, 48, S27-S35.
48. Hespel, P. & Richter, E.A. (1998) Role of adenosine in regulation of carbohydrate metabolism in contracting muscle. Advances in Experimental Medicine and Biology, 44, 97-106.
49. Hinschen, A.K., Rose'Meyer, R.B. & Headrick, J.P. (2000) Age-related changes in A(1)-adenosine receptor-mediated bradycardia. American Journal of Physiology: Heart and Circulatory Physiology, 278, H789-H795.
50. Hoffman, B.B., Chang, H., Farahbakhsh, Z. & Reavan, G. (1984) Inhibition of lipolysis by adenosine is potentiated with age. Journal of Clinical Investigation, 74, 1750-1755.
51. Hudlicka, O., Komarek, J. & Wright, A.J. (1981) The effect of a xanthine derivative, 1-(5′ oxohexyl)-3-methyl-7-propylxanthine (HWA 285), on heart performance and regional blood flow in dogs and rabbits. British Journal of Pharmacology, 72, 723-730.
52. Hug, M.C. & Neu, H. (1995) Clinical and echocardiographic case control study in dogs with heart failure in stages I-III under treatment with Propentofylline (Karsivan). Tierarztliche Praxis Ausgabe K, Kleintiere/ Heinitiere, 26, 317-321.
53. Kaiser, S.M. & Quinn, R.J. (1999) Adenosine receptors as potential therapeutic targets. Drug Discovery Today, 4, 542-551.
54. Kangasniemi, M. (1993) Effects of adenosine analog PIA (n-phenylisopropyladenosine) on FSH-stimulated cyclic AMP (cAMP) production in the rat seminiferous epithelium. Molecular and Cellular Endocrinology, 96, 141-146.
55. Kapl, D. & Rudolphi, K.A. (1998) New pharmacologic aspects in the neurologic profile of propentofylline [Article in German]. Tierarztliche Praxis Ausgabe K, Kleintiere/Heimtiere, 26, 317-321.
56. Killic, S., Salih, M., Anafarta, K., Baltaci, S. & Kosar, A. (1994) Adenosine: a new agent in the diagnosis of impotence. International Journal of Impotence Research, 6, 191-198.
57. Kittner, B. (1999) Clinical trials of propentofylline in vascular dementia. European/Canadian Propentofylline Study Group. Alzheimer Disease and Associated Disorders, 13 (Suppl. 3), 166-171.
58. Kittner, B., Rossner, M. & Rother, M. (1997) Clinical trials in dementia with propentofylline. Annals of the New York Academy of Science, 826, 307-316.
59. Klotz, K.-N. (2000) Adenosine receptors and their ligands. Naumyn-Schmiedeberg's Archives of Pharmacology, 362, 382-391.
60. Koriyama, Y., Yamazaki, M., Chiba, K. & Mohri, T. (2000) Evaluation of neurotoxicity of Alzheimer's amyloid beta protein (beta42) in cultured hippocampal cells and its prevention by propentofylline. Japanese Journal of Pharmacology, 82, 301-306.
61. Latini, S. & Pedata, F. (2001) Adenosine in the central nervous system: release mechanisms and extracellular concentrations. Journal of Neurochemistry, 79, 463-484.
62. Latini, S., Pazzagli, M., Pepeu, G. & Pedata, F. (1996) A2 adenosine receptors: their presence and neuromodulatory role in the central nervous system. General Pharmacology, 27, 925-933.
63. Linden, J. (1994) Cloned adenosine A3 receptors: pharmacological properties, species differences and receptor functions. Trends in Pharmacological Science, 15, 298-306.
64. Linden, J., Auchampach, J.A., Jin, X. & Figle, R.A. (1998) The structure and function of A1 and A2B adenosine receptors. Life Sciences, 62, 1519-1524.
65. Lynge, J. & Hellsten, Y. (2000) Distribution of adenosine A1, A2A and A2B receptors in human skeletal muscle. Acta Physiologica Scandinavia, 169, 283-290.
66. Marcusson, J., Rother, M., Kittner, B., Rossner, M., Smith, R.J., Babic, T., Folnegovic-Smalc, V., Moller, H.J. & Labs, K.H. (1997) A12-month, randomised, placebo-controlled trial of propentofylline (HWA 285) in patients with dementia according to DSM III-R. The European Propentofylline Study Group. Dementia, Geriatrics and Cognitive Disorders, 8, 320-328.
67. Marshall, J.M. (2002) Roles of adenosine in skeletal muscle during systemic hypoxia. Clinical and Experimental Pharmacology and Physiology, 29, 843-849.
68. Mazzoni, M.R., Buffoni, R.S., Giusti, L. & Lucacchini, A. (1995) Characterization of a low affinity binding site for N6-substituted adenosine derivatives in rat testis membranes. Journal of Receptor and Signal Transduction Research, 15, 905-929.
69. Meskini, N., Nemoz, G., Okyayuz-Baklouti, I., Lagarde, M. & Prigent, A.F. (1994) Phosphodiesterase inhibitory profile of some related xanthine derivatives pharmacologically active on the peripheral microcirculation. Biochemical Pharmacology, 47, 781-788.
70. Mielke, R., Moller, H.J., Erkinjuntti, T., Rosenkranz, B., Rother, M. & Kittner, B. (1998) Propentofylline in the treatment of vascular dementia and Alzheimer-type dementia: overview of phase I and II clinical trials. Alzheimer Disease and Associated Disorders 12 (Suppl. 2), S29-S35.
71. Moller, H.J., Maurer, I. & Saletu, B. (1994) Placebo-controlled trial of the xanthine derivative propentofylline in dementia. Pharmacopsychiatry, 27, 159-165.
72. Moreau, J.L. & Huber, G. (1999) Central adenosine A(2A) receptors: an overview. Brain Research Reviews, 31, 65-82.
73. Mosier, J.E. (1989) Effect of ageing on body systems in the dog. Geriatrics and gerontology. Veterinary Clinics of North America: Small Animal Practice, 19, 1-12.
74. Mubagwa, K. & Flameng, W. (2001) Adenosine, adenosine receptors and myocardial protection, an updated overview. Cardiovascular Research, 52, 25-39.
75. Mubagwa, K., Mullane, K. & Flameng, W. (1996) Role of adenosine in the heart and circulation. Cardiovascular Research, 32, 797-813.
76. Muller, C.E. (2001) A1 adenosine receptors and their ligands: overview and recent developments. Farmaco, 56, 77-80.
77. Nagata, K., Ogawa, T., Omosu, M., Fujimoto, K. & Hayashi, S. (1985) In vitro and in vivo inhibitory effects of propentofylline on cyclic AMP, phosphodiesterase activity. Arzneimittelforschung, 35, 1034-1036.
78. Nitahara, K., Kornak, P., Nagashima, H., Vizi, E.S., Foldes, F.F. & Dan, K. (2000) Adenosine potentiation of neuromuscular blocking agents in guinea pigs. British Journal of Anaesthesia, 84, 245-247.
79. Numagami, Y., Marro, P.J., Mishra, O.P. & Delivoria-Papadopoulos, M. (1998) Effect of propentofylline on free radical generation during cerebral hypoxia in the newborn piglet. Neuroscience, 84, 1127-1133.
80. Nyce, J.W. (1999) Insight into adenosine receptor function using antisense and gene-knockout approaches. Trends Pharmacological Science, 20, 79-83.
81. Obata, T. (2002) Adenosine production and its interaction with protection of ischemic and reperfusion injury of the myocardium. Life Sciences, 72, 2083-2103.
82. Olah, M.E. & Stiles, G.L. (2000) The role of receptor structure in determining adenosine receptor activity. Pharmacological Therapeutics, 85, 55-75.
83. Olson, P.N., Kustritz, M.V. & Johnston, S.D. (2001) Early-age neutering of dogs and cats in the United States (a review). Journal of Reproduction and Fertility Supplement, 57, 223-232.
84. Olsson, R.A. & Pearson, J.D. (1990) Cardiovascular purinoceptors. Physiological Reviews, 70, 761-845.
85. Palmer, T.M. & Stiles, G.L. (1995) Adenosine receptors. Neuropharmacology, 34, 683-694.
86. Parkinson, F.E., Paterson, A.R., Young, J.D. & Cass, C.E. (1993) Inhibitory effects of propentofylline on [3H] adenosine influx. A study of three nucleoside transport systems. Biochemical Pharmacology, 46, 891-896.
87. Parkinson, F.E., Rudolphi, K.A. & Fredholm, B.B. (1994) Propentofylline: a nucleoside transport inhibitor with neuroprotective effects in cerebral ischemia. General Pharmacology, 25, 1053-1058.
88. Phillis, J.W. & O'Regan, M.H. (1988) Effects of estradiol on cerebral cortical neurons and their responses to adenosine. Brain Research Bulletin, 20, 151-155.
89. Phillis, J.W., Bender, A.S. & Marszalec, W. (1985) Estradiol and progesterone potentiate adenosine's depressant action on rat cerebral cortical neurons. General Pharmacology, 6, 609-612.
90. Popoli, S., Betto, P., Rimondini, R., Reggio, R., Pezzola, A., Ricciarello, G., Fuxe, K. & Ferre, S. (1998) Age-related alteration of the adenosine/ dopamine balance in the rat striatum. Brain Research, 795, 297-300.
91. Poulsen, S.-A. & Quinn, R.J. (1998) Adenosine receptors: new opportunities for future drugs. Bioorganic and Medicinal Chemistry, 6, 619-641.
92. Ralevic, V. & Burnstock, G. (1998) Receptors for purines and pyridamines. Pharmacological Reviews, 50, 415-492.
93. Ramkumar, V., Hallam, D.M. & Nie, Z. (2001) Adenosine, oxidative stress and cytoprotection. Japanse Journal of Pharmacology, 86, 265-274.
94. Rankin, A.C., Oldroyd, K.G., Chong, E., Rae, A.P. & Cobbe, S.M. (1989) Value and limitations of adenosine in the diagnosis and treatment of narrow and broad complex tachycardias. British Heart Journal, 62, 195-203.
95. Rathbone, M.P., Middlemiss, P.J., Gysbers, J.W., Andrew, C., Herman, M.A., Reed, J.K., Ciccarelli, R., Di Iorio, P. & Caciagli, F. (1999) Trophic effects of purines in neurons and glial cells. Progress in Neurobiology, 59, 663-690.
96. Rees, D.A., Scanlon, M.F. & Ham, J. (2003a) Adenosine signalling pathways in the pituitary gland: one ligand, multiple receptors. Journal of Endocrinology, 177, 357-364.
97. Rees, D.A., Scanlon, M.F. & Ham, J. (2003b) Novel insights into how purines regulate pituitary cell function. Clinical Science (London), 104, 467-481.
98. Ringheim, G.E. (2000) Glial modulating and neurotrophic properties of propentofylline and its application to Alzheimer's disease and vascular dementia. Annals of the New York Academy of Science, 903, 529-534.
99. Rivkees, S.A. (1994) Localization and characterization of adenosine receptor expression in rat testis. Endocrinology, 135, 2307-2313.
100. 2+ entry in the nerve terminal of the frog neuromuscular junction. Canadian Journal of Physiology and Pharmacology, 77, 707-714.
101. Rolband, G.C., Furth, E.D., Staddon, J.M., Rogus, E.M. & Goldberg, A.P. (1990) Effect of age and adenosine in the metabolism of insulin action on rat adipocyte metabolism. Journal of Gerontology, 45, 174-178.
102. Roof, R.L. & Hall, E.D. (2000) Gender differences in acute CNS trauma and stroke: neuroprotective effects of estrogen and progesterone. Journal of Neurotrauma, 17, 367-388.
103. Rose'Meyer, R.B., Harden, F.A., Varela, J.I., Harrison, G.J. & Willis, R.J. (1999) Age-related changes in adenosine in rat coronary resistance vessels. General Pharmacology, 32, 35-40.
104. Rose'Meyer, R.B., Mellick, A.S., Garnham, B.G., Harrison, G.J., Massa, H.M. & Griffiths, L.R. (2003) The measurement of adenosine and estrogen receptor expression in rat brains following ovariectomy using quantitative PCR analysis. Brain Research Protocols, 11, 9-18.
105. Rossignol, L., Plantavid, M., Chap, H. & Douste-Blazy, L. (1988) Effects of two methylxanthines, pentoxifylline and propentofylline, on arachidonic acid metabolism in platelets stimulated by thrombin. Biochemical Pharmacology, 37, 3229-3236.
106. Rother, M., Kittner, B., Rudolphi, K., Rossner, M. & Labs, K.H. (1996) HWA 285 (propentofylline) A new compound for the treatment of both vascular dementia and dementia of the Alzheimer type. Annals of the New York Academy of Science, 777, 404-409.
107. Rother, M., Erkinjuntti, T., Roessner, M., Kittner, B., Marcusson, J. & Karlsson, I. (1998) Propentofylline in the treatment of Alzheimer's disease and vascular dementia: a review of phase III trials. Dementia, Geriatrics and Cognitive Disorders, 9 (Suppl. 1), 36-43.
108. Rudolphi, K.A., Schubert, P., Parkinson, F.E. & Fredholm, B.B. (1992) Adenosine and brain ischemia. Cerebrovascular and Brain Metabolism Reviews, 4, 346-369.
109. Salmeri, K.R., Bloomberg, M.S., Scruggs, S.L. & Shille, V. (1991) Gonadectomy in immature dogs: effects on skeletal, physical, and behavioral development. Journal of the American Veterinary Medical Association, 198, 1193-1203.
110. Schubert, P., Ogata, T., Marchini, C., Ferroni, S. & Rudolphi, K. (1997a) Protective mechanisms of adenosine in neurones and glial cells. Annals of the New York Academy of Science, 825, 1-10.
111. Schubert, P., Ogata, T., Rudolphi, K., Marchini, C., McRae, A. & Ferroni, S. (1997b) Support of homeostatic glial cell signalling: a novel therapeutic approach by propentofylline. Annals of the New York Academy of Science, 826, 337-347.
112. Schwartz, A.D., Whitacre, C.L., Lin, Y. & Wilson, D.F. (2003) Adenosine inhibits N-type calcium channels at the rat neuromuscular junction. Clinical and Experimental Pharmacology and Physiology, 30, 174-177.
113. Sebastião, A.M. & Ribeiro, J.A. (2000) Fine-tuning neuromodulation by adenosine. Trends in Pharmacological Science, 21, 341-346.
114. Seiffge, D. (1997) Pentoxifylline: its influence on the interaction of blood cells with the vessel wall. Atherosclerosis, 131(Suppl.), S27-S28.
115. Seiffge, D. & Katsuyoshi, N. (1985) Effects of propentofylline on the micromechartical properties of red blood cells. Drug Development Research, 5, 147-155.
116. Sitkovsky, M.V. (2003) Use of the A(2A) adenosine receptor as a physiological immunosuppressor and to engineer inflammation in vivo. Biochemical Pharmacology, 65, 493-501.
117. Siwak, C.T., Gruet, P., Woehrle, F., Muggenburg, B.A., Murphy, H.L. & Milgram N.W. (2000) Comparison of the effects of adrafinil, propentofylline, and nicergoline on behavior in aged dogs. American Journal of Veterinary Research, 61, 1410-1414.
118. Spain, C.V., Scarlett, J.M. & Cully, S.M. (2002) When to neuter dogs and cats: a survey of New York state veterinarians' practices and beliefs. Journal of the American Animal Hospital Association, 38, 482-488.
119. Stiles, G.L., Pierson, G., Sunnay, S. & Parsons, W.J. (1986) The rat testicular A1 adenosine receptor-adenylate cyclase system. Endocrinology, 119, 1845-1851.
120. Stocklin-Gautschi, N.M., Hassig, M., Reichler, I.M., Hubler, M. & Arnold, S. (2001) The relationship of urinary incontinence to early spaying in bitches. Journal of Reproduction and Fertility, 57(Suppl.), 233-236.
121. Stone, T.W. (1991) Adenosine as a neuroactive compound in the central nervous system. In Adenosine and Adenine Nucleotides as Regulators of Cellular Function, Ed. Phillis, J.W. pp. 329-338. CRC Press, West Palm Beach, FL.
122. Stone, T.W. (2002) Purines and neuroprotection. Advances in Experimental Medicine and Biology, 513, 249-280. Neuroscience, 113, 709-719.
123. Stone, T.W. (2002) Purines and neuroprotection. Advances in Experimental Medicine and Biology, 513, 249-280. Neuroscience, 113, 709-719.
124. Stubbs, W.P. & Bloomberg, M.S. (1995) Implications of early neutering in the dog and cat. Seminars in Veterinary Medicine and Surgery (Small Animals), 10, 8-12.
125. Takahashi, Y., Ishii, N., Lue, T.F. & Tanagho, E.A. (1991) Pharmacological effects of adenosine on canine penile erection. Tohoku Journal of Expperimental Medicine, 165, 49-58.
126. Takeuchi, T., Yoneyama, Y., Suzuki, S., Sawa, R., Otsubo, Y. & Araki, T. (2001) Regulation of platelet aggregation in vitro by plasma adenosine in preeclampsia. Gynecologic and Obstetric Investigation, 51, 36-39.
127. Thomas, G., Bouchard, P., Schaison, G. & Baulieu, E.E. (1984) The hormonal control of adenylate cyclase in rabbit myometrium: in vitro inhibition by adenosine and lack of effect if progesterone. Molecular and Cellular Endocrinology, 35, 177-182.
128. Thrusfleld, M.V., Holt, P.E. & Muirhead, R.H. (1998) Acquired urinary incontinence in bitches', its incidence and relationship to neutering practices. Journal of Small Animal Practice, 39, 559-566.
129. Timoteo, M.A., Faria, M. & Correia-de-Sa, P. (2003) Endogenous adenosine prevents post-tetanic release facilitation mediated by alpha 3 beta 2 nicotinic autoreceptors. European Journal of Pharmacology, 464, 115-125.
130. Torvinen, M., Gines, S., Hillion, J. et al. (2002) Interactions among adenosine deaminase, adenosine A(1) receptors and dopamine D(1) receptors in stably cotransfected fibroblast cells and neurons. Neuroscience, 113, 709-719.
131. Tsitouras, P.D., Kowatch, M.A. & Harman, S.M. (1979) Age-related alterations of isolated rat leydig cell function: gonadotropin receptors, adenosine 3′,5′-monophosphate response, and testosterone secretion. Endocrinology, 105, 1400-1405.
132. Wardas, J. (2002) Neuroprotective role of adenosine in the CNS. Polish Journal of Pharmacology, 54, 313-326.
133. Welch, W.J. (2002) Adenosine A1 receptor antagonists in the kidney: effects in fluid-retaining disorders. Current Opinions in Pharmacology 2, 165-170.
134. Wise, P.M., Dubal, D.B., Wilson, M.E., Rau, S.W. & Bottner, M. (2001a) Minireview: neuroprotective effects of estrogen - new insights into mechanisms of action. Endocrinology, 142, 969-973.
135. Wise, P.M., Dubal, D.B., Wilson, M.E., Rau, S.W. & Liu, Y. (2001b) Estrogens: trophic and protective effects in the adult brain. Frontiers of Neuroendocrinology, 19, 323-362.
136. Yasuda, N., Inoue, T., Horizo, T. et al. (2003) Functional characterization of the adenosine receptor contributing to glycogenolysis and gluconeogenesis in rat hepatocytes. European Journal of Pharmacology, 459, 159-166.
137. Ynaraja, E., Montoya, A., Caro, A. & Mayoral, I. (1998) Propentofylline. Clinical use of Karsivan in dogs with congestive cardiac insufficiency due to senile mitral valvulopathy: combined treatment regimen using bemethanide perindopril and a sodium-restricted diet. Part 2: results and discussion of clinical study, conclusions and bibliography. Medicina Veterinaria, 15, 462-480.
138. Yoneyama, Y., Suzuki, S., Sawa, R., Kiyokawa, Y. Power, G.G. & Araki, T. (2001) Plasma adenosine levels and P-selectin expression on platelets in preeclampsia. Obstetrics and Gynaecology, 97, 366-370.
139. Zhang, Y. & Fredholm, B.B. (1994) Propentofylline enhancement of the actions of adenosine on neutrophils leukocytes. Biochemical Pharmacology, 48, 2025-2032.
140. Zhong, H., Shlykov, S.G., Molina, J.G., Sanborn, B.M., Jacobson, M.A., Tilley, S.L. & Blackburn, M.R. (2003) Activation of murine lung mast cells by the adenosine A(3) receptor. Journal of Immunology, 171, 338-345.