{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T10:31:38Z","timestamp":1773657098457,"version":"3.50.1"},"reference-count":36,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2009,1,29]],"date-time":"2009-01-29T00:00:00Z","timestamp":1233187200000},"content-version":"vor","delay-in-days":3103,"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":[[2000,8]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>Sphingolipids such as sphingosine\u20101\u2010phosphate (SPP) and sphingosylphosphorylcholine (SPPC) can act both intracellularly and at G\u2010protein\u2010coupled receptors, some of which were cloned and designated as Edg\u2010receptors.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Sphingolipid\u2010induced vascular effects were determined in isolated rat mesenteric and intrarenal microvessels. Additionally, sphingolipid\u2010induced elevations in intracellular Ca<jats:sup>2+<\/jats:sup> concentration were measured in cultured rat aortic smooth muscle cells.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>SPPC and SPP (0.1\u2013100\u2003\u03bcmol\u2003l<jats:sup>\u22121<\/jats:sup>) caused concentration\u2010dependent contraction of mesenteric and intrarenal microvessels (e.g. SPPC in mesenteric microvessels pEC<jats:sub>50<\/jats:sub> 5.63\u00b10.17 and E<jats:sub>max<\/jats:sub> 49\u00b13% of noradrenaline), with other sphingolipids being less active. The vasoconstrictor effect of SPPC in mesenteric microvessels was stereospecific (pEC<jats:sub>50<\/jats:sub> D\u2010<jats:italic>erythro<\/jats:italic>\u2010SPPC 5.69\u00b10.08, L\u2010<jats:italic>threo<\/jats:italic>\u2010SPPC 5.31\u00b10.06) and inhibited by pretreatment with pertussis toxin (E<jats:sub>max<\/jats:sub> from 44\u00b15 to 19\u00b14%), by chelation of extracellular Ca<jats:sup>2+<\/jats:sup> with EGTA and by nitrendipine (E<jats:sub>max<\/jats:sub> from 40\u00b16 to 6\u00b11 and 29\u00b16%, respectively). Mechanical endothelial denudation or NO synthase inhibition did not alter the SPPC effects, while indomethacin reduced them (E<jats:sub>max<\/jats:sub> from 87\u00b13 to 70\u00b14%).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>SPP and SPPC caused transient increases in intracellular Ca<jats:sup>2+<\/jats:sup> concentrations in rat aortic smooth muscle cells in a pertussis toxin\u2010sensitive manner.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Our data demonstrate that SPP and SPPC cause vasoconstriction of isolated rat microvessels and increase intracellular Ca<jats:sup>2+<\/jats:sup> concentrations in cultured rat aortic smooth muscle cells. These effects appear to occur <jats:italic>via<\/jats:italic> receptors coupled to pertussis toxin\u2010sensitive G\u2010proteins. This is the first demonstration of effects of SPP and SPPC on vascular tone and suggests that sphingolipids may be an hitherto unrecognized class of endogenous regulators of vascular tone.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (2000) <jats:bold>130<\/jats:bold>, 1871\u20131877; doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0703515\">10.1038\/sj.bjp.0703515<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0703515","type":"journal-article","created":{"date-parts":[[2005,1,28]],"date-time":"2005-01-28T20:46:59Z","timestamp":1106945219000},"page":"1871-1877","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":89,"title":["Sphingosine\u20101\u2010phosphate and sphingosylphosphorylcholine constrict renal and mesenteric microvessels <i>in vitro<\/i>"],"prefix":"10.1111","volume":"130","author":[{"given":"Angela","family":"Bischoff","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Czyborra","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charlotte","family":"Fetscher","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dagmar","family":"Meyer zu Heringdorf","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karl H","family":"Jakobs","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin C","family":"Michel","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\/S0014-5793(97)01301-X"},{"key":"e_1_2_7_3_1","first-page":"787","article-title":"Transduction of intracellular calcium signals through G protein\u2010mediated activation of phospholipase C by recombinant sphingosine 1\u2010phosphate receptors","volume":"55","author":"AN S.","year":"1999","journal-title":"Mol. 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