{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T20:19:17Z","timestamp":1771532357633,"version":"3.50.1"},"reference-count":41,"publisher":"American Physiological Society","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Cell Physiology"],"published-print":{"date-parts":[[2000,1,1]]},"abstract":"<jats:p> It is commonly believed that the activity of NO synthase (NOS) solely controls NO production from its substrates, l-Arg and O<jats:sub>2<\/jats:sub>. The Michaelis-Menten constant ( K <jats:sub>m<\/jats:sub>) of NOS forl-Arg is in the micromolar range; cellular levels of l-Arg are much higher. However, evidence strongly suggests that cellular supply of l-Arg may become limiting and lead to reduced NO and increased superoxide anion ([Formula: see text]) formation, promoting cardiovascular dysfunction. Uptake ofl-Arg into cells occurs primarily (\u223c85%) through the actions of a Na<jats:sup>+<\/jats:sup>-independent, carrier-mediated transporter (system y<jats:sup>+<\/jats:sup>). We have examined the effects of NOS agonists (substance P, bradykinin, and ACh) and NO donors ( S-nitroso- N-acetyl-penicillamine and dipropylenetriamine NONOate) on transport ofl-Arg into bovine aortic endothelial cells (BAEC). Our results demonstrate that NOS agonists increase y<jats:sup>+<\/jats:sup> transporter activity. A rapidly acting NO donor initially increasesl-Arg uptake; however, after longer exposure, l-Arg uptake is suppressed. Exposure of BAEC withoutl-Arg to substance P and a Ca<jats:sup>2+<\/jats:sup> ionophore (A-23187) increased[Formula: see text] formation, which was blocked with concurrent presence ofl-Arg or the NOS antagonist N <jats:sup>\u03c9<\/jats:sup>-nitro-l-arginine methyl ester. We conclude that factors including NO itself control y<jats:sup>+<\/jats:sup> transport function and the production of NO and [Formula: see text]. <\/jats:p>","DOI":"10.1152\/ajpcell.2000.278.1.c136","type":"journal-article","created":{"date-parts":[[2017,12,24]],"date-time":"2017-12-24T22:34:06Z","timestamp":1514154846000},"page":"C136-C143","source":"Crossref","is-referenced-by-count":50,"title":["Effects of NO donors and synthase agonists on endothelial  cell uptake of <scp>l<\/scp>-Arg and superoxide production"],"prefix":"10.1152","volume":"278","author":[{"given":"Alison A.","family":"Ogonowski","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wayne H.","family":"Kaesemeyer","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liming","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vadivel","family":"Ganapathy","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta, Georgia 30912"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fredrick H.","family":"Leibach","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta, Georgia 30912"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R. 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