{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T18:10:25Z","timestamp":1761675025077},"reference-count":65,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2004,1,17]],"date-time":"2004-01-17T00:00:00Z","timestamp":1074297600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004263","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado do Rio Grande do Sul","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004263","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004809","name":"Financiadora de Estudos e Projetos","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Intl J of Devlp Neuroscience"],"published-print":{"date-parts":[[2004,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label \/><jats:p>In the present study, we investigated the in vitro effect of hypoxanthine, xanthine and uric acid, metabolites accumulating in tissue of patients with Lesch\u2013Nyhan disease, on Na<jats:sup>+<\/jats:sup>, K<jats:sup>+<\/jats:sup>\u2010ATPase activity in striatum of neonate rats. Results showed that all compounds significantly inhibited Na<jats:sup>+<\/jats:sup>, K<jats:sup>+<\/jats:sup>\u2010ATPase activity. We also studied the kinetics of the inhibition of Na<jats:sup>+<\/jats:sup>, K<jats:sup>+<\/jats:sup>\u2010ATPase activity caused by hypoxanthine. The apparent <jats:italic>K<\/jats:italic><jats:sub>m<\/jats:sub> and <jats:italic>V<\/jats:italic><jats:sub>max<\/jats:sub> of Na<jats:sup>+<\/jats:sup>, K<jats:sup>+<\/jats:sup>\u2010ATPase activity for ATP as the substrate and hypoxanthine as the inhibitor were 0.97 mM and 0.69 nmol inorganic phosphate (Pi) released per min per mg of protein, respectively. <jats:italic>K<jats:sub>i<\/jats:sub><\/jats:italic>\u2010value was 1.9 \u03bcM, and the inhibition was of the non\u2010competitive type. We also observed that the inhibitory effects of hypoxanthine, xanthine and uric acid probably occur through the same mechanism, suggesting a common binding site for these oxypurines on Na<jats:sup>+<\/jats:sup>, K<jats:sup>+<\/jats:sup>\u2010ATPase. Therefore, it is conceivable that inhibition of brain Na<jats:sup>+<\/jats:sup>, K<jats:sup>+<\/jats:sup>\u2010ATPase activity may be involved at least in part in the neuronal dysfunction characteristic of patients with Lesch\u2013Nyhan disease.<\/jats:p><\/jats:sec>","DOI":"10.1016\/j.ijdevneu.2003.11.002","type":"journal-article","created":{"date-parts":[[2004,1,20]],"date-time":"2004-01-20T10:18:45Z","timestamp":1074593925000},"page":"11-17","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Inhibition of Na<sup>+<\/sup>, K<sup>+<\/sup>\u2010ATPase activity in rat striatum by the metabolites accumulated in Lesch\u2013Nyhan disease"],"prefix":"10.1002","volume":"22","author":[{"given":"Caren S.","family":"Bavaresco","sequence":"first","affiliation":[{"name":"Departamento de Bioqu\u0131\u0301mica Instituto de Ci\u00eancias B\u00e1sicas da Sa\u00fade Universidade Federal do Rio Grande do Sul Rua Ramiro Barcelos, 2600\u2010Anexo CEP 90035\u2010003 Porto Alegre RS Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexandra I.","family":"Zugno","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u0131\u0301mica Instituto de Ci\u00eancias B\u00e1sicas da Sa\u00fade Universidade Federal do Rio Grande do Sul Rua Ramiro Barcelos, 2600\u2010Anexo CEP 90035\u2010003 Porto Alegre RS Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B\u00e1rbara","family":"Tagliari","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u0131\u0301mica Instituto de Ci\u00eancias B\u00e1sicas da Sa\u00fade Universidade Federal do Rio Grande do Sul Rua Ramiro Barcelos, 2600\u2010Anexo CEP 90035\u2010003 Porto Alegre RS Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cl\u00f3vis M.D.","family":"Wannmacher","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u0131\u0301mica Instituto de Ci\u00eancias B\u00e1sicas da Sa\u00fade Universidade Federal do Rio Grande do Sul Rua Ramiro Barcelos, 2600\u2010Anexo CEP 90035\u2010003 Porto Alegre RS Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Moacir","family":"Wajner","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u0131\u0301mica Instituto de Ci\u00eancias B\u00e1sicas da Sa\u00fade Universidade Federal do Rio Grande do Sul Rua Ramiro Barcelos, 2600\u2010Anexo CEP 90035\u2010003 Porto Alegre RS Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angela T.S.","family":"Wyse","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u0131\u0301mica Instituto de Ci\u00eancias B\u00e1sicas da Sa\u00fade Universidade Federal do Rio Grande do Sul Rua Ramiro Barcelos, 2600\u2010Anexo CEP 90035\u2010003 Porto Alegre RS Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2004,1,17]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.78.11.6858"},{"key":"e_1_2_6_3_1","first-page":"1655","volume-title":"The Metabolic and Molecular Basis of Inherited Disease","author":"Becker M.A.","year":"1995"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(85)90299-4"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.1969.00480070054006"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(76)90527-3"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.1995.tb00689.x"},{"key":"e_1_2_6_8_1","first-page":"129","article-title":"Interactions of tricyclic drug analogs with synaptic plasma membranes: structure\u2013mechanism relationships in inhibition of neuronal Na+, \/K+, \u2010ATPase activity","volume":"44","author":"Carfagna M.A.","year":"1993","journal-title":"Mol. Pharmacol."},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(86)90640-8"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.34.3.315"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj2890599"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.ne.13.030190.001131"},{"key":"e_1_2_6_13_1","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1016\/0361-9230(94)90285-2","article-title":"Uric acid is reduced in the substantia nigra in Parkinson's disease: effect on dopamine oxidation","volume":"33","author":"Church W.H.","year":"1999","journal-title":"Brain Res. Bull."},{"key":"e_1_2_6_14_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0014-2999(92)90454-C","article-title":"Differential effects of various xanthines on pentyletetrazole\u2010induced seizures in rats: an EEG and behavioral study","volume":"3","author":"Cutrufo C.","year":"1992","journal-title":"Eur. J. Pharmacol."},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0736-5748(02)00109-0"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(03)03029-4"},{"key":"e_1_2_6_17_1","first-page":"21","article-title":"Ions and energy in mammalian brain","volume":"7","author":"Erecinska M.","year":"1994","journal-title":"Prog. Neurobiol."},{"key":"e_1_2_6_18_1","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/0306-9877(92)90026-9","article-title":"Serotonin\u2010gaba treatment is hypothesized for self\u2010injury in Lesch\u2013Nyhan syndrome","volume":"38","author":"Geyde A.","year":"1992","journal-title":"Med. Hypoth."},{"key":"e_1_2_6_19_1","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1002\/ana.410160719","article-title":"Glial and neuronal Na+, K+, \u2010pump in epilepsy","volume":"16","author":"Grisar T.","year":"1984","journal-title":"Ann. Neurol."},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.1987.tb03419.x"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3940(98)00654-5"},{"key":"e_1_2_6_22_1","first-page":"302","article-title":"Possible functions of hypoxanthine\u2013guanine hosphoribosyltransferase and their relation to the biochemical pathology of the Lesch\u2013Nyhan syndrome","volume":"2","author":"Herderson J.F.","year":"1968","journal-title":"Fed. Proc."},{"key":"e_1_2_6_23_1","first-page":"2537","volume-title":"The Metabolic and Molecular Bases of Inherited Disease","author":"Jinnah H.A.","year":"2001"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/0361-9230(90)90239-V"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/0005-2736(74)90268-5"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1053\/snep.2001.21665"},{"key":"e_1_2_6_27_1","first-page":"400","article-title":"Inhibition of a membrane Na+, K+, \u2010ATPase activity: a common pathway in central nervous system disorder","volume":"50","author":"Kumar A.R.","year":"2002","journal-title":"J. Assoc. Physicians India"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(93)90254-D"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.1044"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/0387-7604(94)90026-4"},{"key":"e_1_2_6_31_1","first-page":"439","article-title":"A familial disorder or uric acid metabolism and central nervous system function II","volume":"67","author":"Nyhan W.L.","year":"1965","journal-title":"J. Pediatr."},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1005348504512"},{"key":"e_1_2_6_33_1","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1007\/978-1-4684-5673-8_27","article-title":"Hypoxanthine accumulation and dopamine depletion in Lesch\u2013Nyhan disease","volume":"253","author":"Palmour R.M.","year":"1989","journal-title":"Adv. Exp. Med. Biol."},{"key":"e_1_2_6_34_1","first-page":"87","article-title":"Xanthine oxidase: biochemistry, distribution and physiology","volume":"548","author":"Parks D.A.","year":"1986","journal-title":"Acta Physiol. Scand."},{"key":"e_1_2_6_35_1","first-page":"1321","article-title":"Proline administration decreases Na+, K+, \u2010ATPase activity in the synaptic plasma membrane from cerebral cortex of rats","volume":"26","author":"Pontes Z.L.","year":"1999","journal-title":"Metab. Brain Res."},{"key":"e_1_2_6_36_1","doi-asserted-by":"crossref","first-page":"1321","DOI":"10.1023\/A:1014201601996","article-title":"Inhibition of Na+, K+, \u2010ATPase activity from rat hippocampus by proline","volume":"26","author":"Pontes Z.L.","year":"2001","journal-title":"Neurochem. Res."},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/0026-0495(89)90189-3"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1157.1992.tb02283.x"},{"key":"e_1_2_6_39_1","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1007\/BF00271165","article-title":"Partial hypoxanthine\u2010guanine phosphoribosyl\u2010transferase deficiency with full expression of the Lesch\u2013Nyhan syndrome","volume":"57","author":"Rijksen G.","year":"1981","journal-title":"Hum. Gen."},{"key":"e_1_2_6_40_1","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1001\/jama.1967.03130160049007","article-title":"Inherited disorder of purine metabolism","volume":"202","author":"Rosenbloom R.M.","year":"1967","journal-title":"JAMA"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0387-7604(00)00143-1"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1515\/jpme.1995.23.3.167"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1651-2227.1981.tb16564.x"},{"key":"e_1_2_6_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(99)01671-6"},{"key":"e_1_2_6_45_1","first-page":"4839","article-title":"Dopamine, serotonin and tachykinin in self\u2010injurious behavior","volume":"14","author":"Sivam S.P.","year":"1996","journal-title":"Life Sci."},{"key":"e_1_2_6_46_1","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1023\/A:1013907104585","article-title":"Inhibition of Na+, K+, \u2010ATPase activity induced by homocysteine id probably mediated by oxidative stress","volume":"26","author":"Streck E.L.","year":"2001","journal-title":"Neurochem. Res."},{"key":"e_1_2_6_47_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1021670607647"},{"key":"e_1_2_6_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0925-4439(03)00019-X"},{"key":"e_1_2_6_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0197-0186(02)00230-9"},{"key":"e_1_2_6_50_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1023815119931"},{"key":"e_1_2_6_51_1","doi-asserted-by":"publisher","DOI":"10.3109\/03009748709102932"},{"key":"e_1_2_6_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(80)90277-4"},{"key":"e_1_2_6_53_1","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1042\/bj2200301","article-title":"Influence of phosphatidylserine on (Na+, K+)\u2010stimulated ATPase and acetylcholinesterase activities of dog brain synaptosomal plasma membranes","volume":"22","author":"Tsakiris S.","year":"1984","journal-title":"Biochem. J."},{"key":"e_1_2_6_54_1","doi-asserted-by":"crossref","first-page":"912","DOI":"10.1111\/j.1651-2227.1996.tb14186.x","article-title":"Altered Na+, K+, \u2010ATPase activity in uraemic adolescents","volume":"85","author":"Vasarhelyi B.","year":"1996","journal-title":"Acta Pediatr."},{"key":"e_1_2_6_55_1","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1016\/S0165-0173(99)00094-6","article-title":"Lesch\u2013Nyhan disease and the basal ganglia","volume":"32","author":"Visser J.E.","year":"2000","journal-title":"Brain Res. Bull."},{"key":"e_1_2_6_56_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.00420"},{"key":"e_1_2_6_57_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.0000081983.34771.D2"},{"key":"e_1_2_6_58_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.2.742"},{"key":"e_1_2_6_59_1","doi-asserted-by":"crossref","first-page":"227S","DOI":"10.1042\/bst023227s","article-title":"Alanine reverses the inhibitory effect of phenylalanine and its metabolites on Na+, K+, \u2010ATPase activity in synaptic plasma membranes from cerebral cortex of rats","volume":"23","author":"Wyse A.T.S.","year":"1995","journal-title":"Biochem. Soc. Trans."},{"key":"e_1_2_6_60_1","first-page":"141","article-title":"Kinetics of alanine reversal on the inhibition of Na+, K+, \u2010ATPase activity by phenylalanine and phenyllactate in the synaptic plasma membrane from the cerebral cortex of rats","volume":"26","author":"Wyse A.T.S.","year":"1998","journal-title":"Med. Sci. Res."},{"key":"e_1_2_6_61_1","first-page":"969","article-title":"Preconditioning prevents the inhibition of Na+, K+, \u2010ATPase activity after brain ischemia","volume":"25","author":"Wyse A.T.S.","year":"2000","journal-title":"Neurochem. Res."},{"key":"e_1_2_6_62_1","doi-asserted-by":"publisher","DOI":"10.1097\/00001756-200007140-00052"},{"key":"e_1_2_6_63_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1010912929042"},{"key":"e_1_2_6_64_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.22-04-01350.2002"},{"key":"e_1_2_6_65_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4547(19980901)53:5<613::AID-JNR11>3.0.CO;2-1"},{"key":"e_1_2_6_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0736-5748(03)00038-8"}],"container-title":["International Journal of Developmental Neuroscience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0736574803001394?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0736574803001394?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1016%2Fj.ijdevneu.2003.11.002","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1016\/j.ijdevneu.2003.11.002","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1016\/j.ijdevneu.2003.11.002","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1016\/j.ijdevneu.2003.11.002","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,7]],"date-time":"2023-09-07T06:18:41Z","timestamp":1694067521000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1016\/j.ijdevneu.2003.11.002"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,1,17]]},"references-count":65,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2004,2]]}},"alternative-id":["10.1016\/j.ijdevneu.2003.11.002"],"URL":"https:\/\/doi.org\/10.1016\/j.ijdevneu.2003.11.002","archive":["Portico"],"relation":{},"ISSN":["0736-5748","1873-474X"],"issn-type":[{"value":"0736-5748","type":"print"},{"value":"1873-474X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2004,1,17]]},"assertion":[{"value":"2003-10-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2003-11-20","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2004-01-17","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}