{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T15:15:05Z","timestamp":1790867705926,"version":"4.1.0"},"reference-count":37,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2006,10,4]],"date-time":"2006-10-04T00:00:00Z","timestamp":1159920000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2006,10,15]]},"abstract":"<jats:p>Endothelial \u03b2<jats:sub>2<\/jats:sub>\u2010adrenoceptor (\u03b2<jats:sub>2<\/jats:sub>AR) stimulation increases nitric oxide (NO) generation, but the underlying cellular mechanisms are unclear. We examined the role of <jats:sc>l<\/jats:sc>\u2010arginine transport and of phosphorylation of NO synthase 3 (NOS\u20103) in \u03b2<jats:sub>2<\/jats:sub>AR\u2010mediated NO biosynthesis by human umbilical vein endothelial cells (HUVEC). To this end, we assessed <jats:sc>l<\/jats:sc>\u2010arginine uptake, NOS activity (from <jats:sc>l<\/jats:sc>\u2010arginine to <jats:sc>l<\/jats:sc>\u2010citrulline conversion), membrane potential (using [<jats:sup>3<\/jats:sup>H]tetraphenylphosphonium), as well as serine phosphorylation of NOS\u20103 (by Western blotting and mass spectrometry), in HUVEC treated with \u03b2AR agonists or cyclic AMP\u2010elevating agents. \u03b2<jats:sub>2<\/jats:sub>AR stimulation increased <jats:sc>l<\/jats:sc>\u2010arginine transport, as did cyclic AMP elevation with either forskolin or dibutyryl cyclic AMP, and this increase was inhibitable by <jats:italic>N<\/jats:italic>\u2010ethylmaleimide. Blockade of <jats:sc>l<\/jats:sc>\u2010arginine uptake by <jats:sc>l<\/jats:sc>\u2010lysine inhibited NOS activity and, conversely, blockade of NOS using <jats:italic>N<\/jats:italic><jats:sup>\u03c9<\/jats:sup>\u2010nitro\u2010<jats:sc>l<\/jats:sc>\u2010arginine methyl ester (<jats:sc>l<\/jats:sc>\u2010NAME) inhibited <jats:sc>l<\/jats:sc>\u2010arginine transport. \u03b2<jats:sub>2<\/jats:sub>AR stimulation also caused a membrane hyperpolarization inhibitable by <jats:sc>l<\/jats:sc>\u2010NAME, suggesting that the increase in <jats:sc>l<\/jats:sc>\u2010arginine uptake occurred in response to NO\u2010mediated hyperpolarization. \u03b2<jats:sub>2<\/jats:sub>AR activation also increased NOS activity and phosphorylation of NOS\u20103 on serine\u20101177, and these increases were attenuated by inhibition of protein kinase A (PKA), phosphatidylinositol 3\u2010kinase (PI3K) or Akt, and abolished by coinhibition of PKA and Akt. These findings suggest that \u03b2<jats:sub>2<\/jats:sub>AR\u2010mediated NOS\u20103 activation in HUVEC is mediated through phosphorylation of NOS\u20103 on serine\u20101177 through both the PKA and the PI3K\/Akt systems, and is sustained by an increase in <jats:sc>l<\/jats:sc>\u2010arginine uptake resulting from NO\u2010mediated membrane hyperpolarization.<\/jats:p>","DOI":"10.1113\/jphysiol.2006.115998","type":"journal-article","created":{"date-parts":[[2006,7,28]],"date-time":"2006-07-28T00:15:02Z","timestamp":1154045702000},"page":"585-594","source":"Crossref","is-referenced-by-count":52,"title":["Mechanisms underlying \u03b2<sub>2<\/sub>\u2010adrenoceptor\u2010mediated nitric oxide generation by human umbilical vein endothelial cells"],"prefix":"10.1113","volume":"576","author":[{"given":"Lindsay R.","family":"Queen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Ji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Biao","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lora","family":"Young","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kang","family":"Yao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda W.","family":"Wyatt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Rowlands","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard C. 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