{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T10:10:24Z","timestamp":1762251024542},"reference-count":29,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2009,1,29]],"date-time":"2009-01-29T00:00:00Z","timestamp":1233187200000},"content-version":"vor","delay-in-days":3072,"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":[[2000,9]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item>\n<jats:p>Previous studies have shown that \u03b2\u2010adrenoceptor antagonists may be substrates of organic cation transporters in kidney and lung. In this study we examined the transport of the \u03b2\u2010adrenoreceptor antagonists propranolol and metoprolol, in renal LLC\u2010PK<jats:sub>1<\/jats:sub> cell monolayers.<\/jats:p>\n<\/jats:list-item>\n<jats:list-item>\n<jats:p>Experiments with BCECF (2\u2032,7\u2032\u2010<jats:italic>bis<\/jats:italic>(2carboxyethyl)\u20105(6)\u2010carboxyfluorescein) loaded LLC\u2010PK<jats:sub>1<\/jats:sub> cell monolayers demonstrated that metoprolol and propranolol flux across the basolateral membrane was consistent with non\u2010ionic diffusion. Flux across the apical membrane consisted of both non\u2010ionic diffusion and the uptake of the cationic form of the \u03b2\u2010adrenoceptor antagonists.<\/jats:p>\n<\/jats:list-item>\n<jats:list-item>\n<jats:p>Uptake of the cationic form of metoprolol across the apical membrane was Na<jats:sup>+<\/jats:sup>\u2010independent, electrogenic and sensitive to external pH. Furthermore, uptake was sensitive to inhibition by Decynium\u201022 and the organic cations TEA (tetraethylammonium) and MPP<jats:sup>+<\/jats:sup> (1\u2010methyl 4\u2010phenylpyridinium). These results, allied with the apical location of the uptake mechanism suggest that \u03b2\u2010adrenoceptor antagonists may be substrates for the organic cation transporter, OCT2.<\/jats:p>\n<\/jats:list-item>\n<jats:list-item>\n<jats:p>To confirm \u03b2\u2010adrenoceptor antagonists as substrates for OCT2, we demonstrate, in cells transiently transfected with an epitope tagged version of hOCT2 (hOCT2\u2010V5):(1) Decynium\u201022 sensitive [<jats:sup>14<\/jats:sup>C]\u2010propranolol uptake, (2) cis\u2010inhibition of OCT2 by a range of \u03b2\u2010adrenoceptor antagonists and (3) metoprolol induced intracellular acidification.<\/jats:p>\n<\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (2000) <jats:bold>131<\/jats:bold>, 71\u201379; doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0703518\">10.1038\/sj.bjp.0703518<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0703518","type":"journal-article","created":{"date-parts":[[2005,1,28]],"date-time":"2005-01-28T20:46:59Z","timestamp":1106945219000},"page":"71-79","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":65,"title":["The organic cation transporter OCT2 mediates the uptake of <i>\u03b2<\/i>\u2010adrenoceptor antagonists across the apical membrane of renal LLC\u2010PK<sub>1<\/sub> cell monolayers"],"prefix":"10.1111","volume":"131","author":[{"given":"Adam J","family":"Dudley","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kelly","family":"Bleasby","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Colin D A","family":"Brown","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","first-page":"S41","article-title":"Functional expression of an epitope tagged version of the human organic cation transporter hOCT2 in mIMCD3 cells","volume":"520","author":"BLEASBY K.","year":"1999","journal-title":"J. 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