{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T22:27:58Z","timestamp":1758925678828},"reference-count":44,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2009,1,29]],"date-time":"2009-01-29T00:00:00Z","timestamp":1233187200000},"content-version":"vor","delay-in-days":3591,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[1999,4]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item>\n<jats:p>Differentiation of SH\u2010SY5Y neuroblastoma cells induces morphological and biochemical changes consistent with a more neuronal phenotype. These cells may therefore provide a model for studying phenomena such as signal transduction in a neuronal context whilst retaining the advantages of a homogenous cell population expressing a well characterized array of G\u2010protein coupled receptors.<\/jats:p>\n<\/jats:list-item>\n<jats:list-item>\n<jats:p>This study examined the effects of differentiating SH\u2010SY5Y cells on muscarinic\u2010 and bradykinin\u2010receptor\u2010mediated phosphoinositide and Ca<jats:sup>2+<\/jats:sup> signalling. Retinoic acid (10\u2003\u03bc<jats:sc>M<\/jats:sc>, 6 days) along with a lowered serum concentration produced phenotypic changes consistent with differentiation including reduced proliferation and increased neurite outgrowth.<\/jats:p>\n<\/jats:list-item>\n<jats:list-item>\n<jats:p>Differentiation increased the magnitude and potency of rapid Ins(1,4,5)P<jats:sub>3<\/jats:sub> responses to a full muscarinic receptor agonist. Bradykinin receptor\u2010mediated Ins(1,4,5)P<jats:sub>3<\/jats:sub> signalling was also potentiated following differentiation. Determination of agonist\u2010evoked accumulation of [<jats:sup>3<\/jats:sup>H]\u2010inositol phosphates under lithium\u2010block demonstrated these changes reflected enhanced phospholipase\u2003C activity which is consistent with observed increases in the expression of muscarinic and bradykinin receptors.<\/jats:p>\n<\/jats:list-item>\n<jats:list-item>\n<jats:p>Despite the marked alterations in Ins(1,4,5)P<jats:sub>3<\/jats:sub> signalling following differentiation, elevations of intracellular [Ca<jats:sup>2+<\/jats:sup>] were totally unaltered. Thus, in SH\u2010SY5Y cells, the relationship between the elevations of Ins(1,4,5)P<jats:sub>3<\/jats:sub> and intracellular [Ca<jats:sup>2+<\/jats:sup>] is agonist dependent and affected by the state of differentiation. This demonstrates that mechanisms other than the measured increase in Ins(1,4,5)P<jats:sub>3<\/jats:sub> regulate the elevation of intracellular [Ca<jats:sup>2+<\/jats:sup>].<\/jats:p>\n<\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (1999) <jats:bold>126<\/jats:bold>, 1559\u20131566; doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0702464\">10.1038\/sj.bjp.0702464<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0702464","type":"journal-article","created":{"date-parts":[[2005,1,28]],"date-time":"2005-01-28T19:58:48Z","timestamp":1106942328000},"page":"1559-1566","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Complex relationship between Ins(1,4,5)P<sub>3<\/sub> accumulation and Ca<sup>2+<\/sup>\u2010signalling in a human neuroblastoma revealed by cellular differentiation"],"prefix":"10.1111","volume":"126","author":[{"given":"Amanda K","family":"Martin","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefan R","family":"Nahorski","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gary B","family":"Willars","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2009,1,29]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-3806(87)90156-8"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1994.62041310.x"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1989.tb12681.x"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/361315a0"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/351751a0"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.50.32366"},{"key":"e_1_2_7_8_1","first-page":"269","article-title":"Heterogeneity of [3H]inositol 1,4,5\u2010trisphosphate binding sites in adrenal cortical membranes. 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