{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T09:07:15Z","timestamp":1773306435763,"version":"3.50.1"},"reference-count":31,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2009,2,5]],"date-time":"2009-02-05T00:00:00Z","timestamp":1233792000000},"content-version":"vor","delay-in-days":4114,"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":[[1997,11]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>The blood\u2010brain barrier is formed by capillary endothelial cells and is regulated by cell\u2010surface receptors, such as the G protein\u2010coupled P2Y receptors for nucleotides. Here we investigated some of the characteristics of control of brain endothelial cells by these receptors, characterizing the phospholipase C and Ca<jats:sup>2+<\/jats:sup> response and investigating the possible involvement of mitogen\u2010activated protein kinases (MAPK).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Using an unpassaged primary culture of rat brain capillary endothelial cells we showed that ATP, UTP and 2\u2010methylthio ATP (2MeSATP) give similar and substantial increases in cytosolic Ca<jats:sup>2+<\/jats:sup>, with a rapid rise to peak followed by a slower decline towards basal or to a sustained plateau. Removal of extracellular Ca<jats:sup>2+<\/jats:sup> had little effect on the peak Ca<jats:sup>2+<\/jats:sup>\u2010response, but resulted in a more rapid decline to basal. There was no response to \u03b1,\u03b2\u2010MethylATP (\u03b1,\u03b2MeATP) in these unpassaged cells, but a response to this P2X agonist was seen after a single passage.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>ATP (log EC<jats:sub>50<\/jats:sub> \u22125.1\u00b10.2) also caused an increase in the total [<jats:sup>3<\/jats:sup>H]\u2010inositol (poly)phosphates ([<jats:sup>3<\/jats:sup>H]\u2010InsP<jats:sub>x<\/jats:sub>) in the presence of lithium with a rank order of agonist potency of ATP=UTP=UDP&gt;ADP, with 2MeSATP and \u03b1,\u03b2MeATP giving no detectable response.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Stimulating the cells with ATP or UTP gave a rapid rise in the level of inositol 1,4,5\u2010trisphosphate (Ins(1,4,5)P<jats:sub>3<\/jats:sub>), with a peak at 10\u2003s followed by a decline to a sustained plateau phase. 2MeSATP gave no detectable increase in the level of Ins(1,4,5)P<jats:sub>3<\/jats:sub>.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>None of the nucleotides tested affected basal cyclic AMP, while ATP and ATP\u03b3S, but not 2MeSATP, stimulated cyclic AMP levels in the presence of 5\u2003\u03bc<jats:sc>M<\/jats:sc> forskolin.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Both UTP and ATP stimulated tyrosine phosphorylation of p42 and p44 mitogen\u2010activated protein kinase (MAPK), while 2MeSATP gave a smaller increase in this index of MAPK activation. By use of a peptide kinase assay, UTP gave a substantial increase in MAPK activity with a concentration\u2010dependency consistent with activation at P2Y<jats:sub>2<\/jats:sub> receptors. 2MeSATP gave a much smaller response with a lower potency than UTP.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>These results are consistent with brain endothelial regulation by P2Y<jats:sub>2<\/jats:sub> receptors coupled to phospholipase C, Ca<jats:sup>2+<\/jats:sup> and MAPK; and by P2Y<jats:sub>1<\/jats:sub>\u2010like (2MeSATP\u2010sensitive) receptors which are linked to Ca<jats:sup>2+<\/jats:sup> mobilization by a mechanism apparently independent of agonist stimulated Ins (1,4,5)P<jats:sub>3<\/jats:sub> levels. A further response to ATP, acting at an undefined receptor, caused an increase in cyclic AMP levels in the presence of forskolin. The differential MAPK coupling of these receptors suggests that they exert fundamentally distinct influences over brain endothelial function.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (1997) <jats:bold>122<\/jats:bold>, 935\u2013941; doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0701453\">10.1038\/sj.bjp.0701453<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0701453","type":"journal-article","created":{"date-parts":[[2005,1,28]],"date-time":"2005-01-28T19:15:39Z","timestamp":1106939739000},"page":"935-941","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":75,"title":["Regulation of brain capillary endothelial cells by P2Y receptors coupled to Ca<sup>2+<\/sup>, phospholipase C and mitogen\u2010activated protein kinase"],"prefix":"10.1111","volume":"122","author":[{"given":"Jennifer L.","family":"Albert","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John P.","family":"Boyle","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan A.","family":"Roberts","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R. 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