{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T21:21:51Z","timestamp":1791148911156,"version":"4.1.0"},"reference-count":31,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2005,12,8]],"date-time":"2005-12-08T00:00:00Z","timestamp":1134000000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2006,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Defect of the purine salvage enzyme, hypoxanthine phosphoribosyl transferase (HPRT), results in Lesch\u2013Nyhan disease (LND). It is unknown how the metabolic defect translates into the severe neuropsychiatric phenotype characterized by self\u2010injurious behavior, dystonia and mental retardation. There are abnormalities in GTP, UTP and CTP concentrations in HPRT\u2010deficient cells. Moreover, GTP, ITP, XTP, UTP and CTP differentially support G<jats:sub>s<\/jats:sub>\u2010protein\u2010mediated adenylyl cyclase (AC) activation. Based on these findings we hypothesized that abnormal AC regulation may constitute the missing link between HPRT deficiency and the neuropsychiatric symptoms in LND. To test this hypothesis, we studied AC activity in membranes from primary human skin and immortalized mouse skin fibroblasts, mouse Neuro\u20102a neuroblastoma cells and rat B103 neuroblastoma cells. In B103 control membranes, GTP, ITP, XTP and UTP exhibited profound stimulatory effects on basal AC activity that approached the effects of hydrolysis\u2010resistant nucleotide analogs. In HPRT<jats:sup>\u2013<\/jats:sup>membranes, the stimulatory effects of GTP, ITP, XTP and UTP were strongly reduced. Similarly, in human and mouse skin fibroblast membranes we also observed a decrease in GTP\u2010stimulated AC activity in HPRT\u2010deficient cells compared with the respective controls. In mouse Neuro\u20102a neuroblastoma membranes, AC activity in the presence of GTP was below the detection limit of the assay. We discuss several possibilities to explain the abnormalities in AC regulation in HPRT deficiency that encompass various species and cell types.<\/jats:p>","DOI":"10.1111\/j.1471-4159.2005.03570.x","type":"journal-article","created":{"date-parts":[[2005,12,8]],"date-time":"2005-12-08T18:06:17Z","timestamp":1134065177000},"page":"454-459","source":"Crossref","is-referenced-by-count":16,"title":["Decreased GTP\u2010stimulated adenylyl cyclase activity in HPRT\u2010deficient human and mouse fibroblast and rat B103 neuroblastoma cell membranes"],"prefix":"10.1111","volume":"96","author":[{"given":"Cibele S.","family":"Pinto","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roland","family":"Seifert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2005,12,8]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(90)90423-7"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1385\/JMN:14:1-2:087"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(01)02909-2"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.2000.279.3.F400"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj20020148"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M211292200"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0005-2736(03)00174-3"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M204259200"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.bi.56.070187.003151"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.0022-3042.2001.00746.x"},{"key":"e_1_2_6_12_1","volume-title":"The Metabolic Basis of Inherited Disease","author":"Jinnah H. 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