{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T02:51:54Z","timestamp":1780455114256,"version":"3.54.1"},"reference-count":38,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2019,4,22]],"date-time":"2019-04-22T00:00:00Z","timestamp":1555891200000},"content-version":"vor","delay-in-days":0,"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":[[2020,2]]},"abstract":"<jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>Among the three enzymes involved in the transsulfuration pathway, only cystathionine \u03b2\u2010synthase (CBS) converts L\u2010cysteine into L\u2010serine and H<jats:sub>2<\/jats:sub>S. L\u2010serine is also involved in the de novo sphingolipid biosynthesis through a condensation with palmitoyl\u2010CoA by the action of serine palmitoyltransferase (SPT). Here, we have investigated if L\u2010serine contributes to the vasorelaxant effect.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>The presence of CBS in mouse vascular endothelium was assessed by immunohistochemistry and immunofluorescence. The relaxant activity of L\u2010serine (0.1\u2013300\u00a0\u03bcM) and L\u2010cysteine (0.1\u2013300\u00a0\u03bcM) was estimated on mouse aorta rings, with or without endothelium. A pharmacological modulation study evaluated NO and sphingosine\u20101\u2010phosphate (S1P) involvement. Levels of NO and S1P were also measured following incubation of aorta tissue with either L\u2010serine (1, 10, and 100\u00a0\u03bcM) or L\u2010cysteine (10, 100\u00a0\u03bcM, and 1\u00a0mM).<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>L\u2010serine relaxed aorta rings in an endothelium\u2010dependent manner. The vascular effect was reduced by L\u2010NG\u2010nitro\u2010arginine methyl ester and wortmaninn. A similar pattern was obtained with L\u2010cysteine. The S1P1 receptor antagonist (W146) or the SPT inhibitor (myriocin) reduced either L\u2010serine or L\u2010cysteine relaxant effect. L\u2010serine or L\u2010cysteine incubation increased NO and S1P levels in mouse aorta.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>L\u2010serine, a by\u2010product formed within the transsulfuration pathway starting from L\u2010cysteine via CBS, contributes to the vasodilator action of L\u2010cysteine. The L\u2010serine effect involves both NO and S1P. This mechanism could be involved in the marked dysregulation of vascular tone in hyperhomocysteinemic patients (CBS deficiency) and may represent a feasible therapeutic target.<\/jats:p><\/jats:sec><jats:sec><jats:title>Linked Articles<\/jats:title><jats:p>This article is part of a themed section on Hydrogen Sulfide in Biology &amp; Medicine. To view the other articles in this section visit <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bph.v177.4\/issuetoc\">http:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bph.v177.4\/issuetoc<\/jats:ext-link><\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.14654","type":"journal-article","created":{"date-parts":[[2019,3,6]],"date-time":"2019-03-06T04:22:55Z","timestamp":1551846175000},"page":"734-744","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["L\u2010cysteine\/cystathionine\u2010\u03b2\u2010synthase\u2010induced relaxation in mouse aorta involves a L\u2010serine\/sphingosine\u20101\u2010phosphate\/NO pathway"],"prefix":"10.1111","volume":"177","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4372-9611","authenticated-orcid":false,"given":"Emma","family":"Mitidieri","sequence":"first","affiliation":[{"name":"Department of Pharmacy, School 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