{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,7]],"date-time":"2026-03-07T15:07:11Z","timestamp":1772896031958,"version":"3.50.1"},"reference-count":36,"publisher":"Wiley","issue":"13","license":[{"start":{"date-parts":[[2004,10,1]],"date-time":"2004-10-01T00:00:00Z","timestamp":1096588800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2004,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Organ\u2010specific overexpression of type 2\n                    <jats:sc>l<\/jats:sc>\n                    \u2010amino acid transporter (LAT2) in the kidney of the spontaneous hypertensive rat (SKR), accompanied by an enhanced ability to take up\n                    <jats:sc>l\u2010DOPA,<\/jats:sc>\n                    may constitute the basis for the enhanced renal production of dopamine in the SHR in an attempt overcome the deficient dopamine\u2010mediated natriuresis. To understand the physiological role of LAT2\u2010mediated\n                    <jats:sc>l\u2010DOPA<\/jats:sc>\n                    handling, we used 21\u2010nucleotide small interfering RNA duplexes (siRNA) to specifically suppress LAT2 expression in LLC\u2010PK\n                    <jats:sub>1<\/jats:sub>\n                    cells, a cell line that retains several properties of proximal tubular epithelial cells and takes up\n                    <jats:sc>l\u2010<\/jats:sc>\n                    DOPA largely through Na\n                    <jats:sup>+<\/jats:sup>\n                    \u2010independent transporters. After cloning the LLC\u2010PK\n                    <jats:sub>1<\/jats:sub>\n                    LAT2 gene, one target region of LAT2 mRNA (nt 97\u2010117) was selected by scanning the length of the LAT2 gene for AA\u2010dinucleotide sequences and downstream 19 nucleotides. Levels of LAT2\n                    <jats:sc>cDNA,<\/jats:sc>\n                    determined by real\u2010time quantitative\n                    <jats:sc>RT\u2010PCR,<\/jats:sc>\n                    were markedly\n                    <jats:sc>(<\/jats:sc>\n                    <jats:italic>\n                      <jats:sc>P<\/jats:sc>\n                    <\/jats:italic>\n                    <jats:sc>&lt;0.05)<\/jats:sc>\n                    reduced by LAT2 siRNA but not by the mismatch LAT2 siRNA. The LAT2 siRNA but not the mismatch LAT2 siRNA, reduced by 85%\n                    <jats:sc>\n                      [\n                      <jats:sup>14<\/jats:sup>\n                      C]\u2010l\u2010DOPA\n                    <\/jats:sc>\n                    accumulation, a time\u2010 and concentration\u2010dependent effect. The efflux of intracellular\n                    <jats:sc>\n                      [\n                      <jats:sup>14<\/jats:sup>\n                      C]\u2010l\u2010DOPA\n                    <\/jats:sc>\n                    was markedly increased\n                    <jats:sc>(<\/jats:sc>\n                    <jats:bold>\n                      <jats:sc>P<\/jats:sc>\n                    <\/jats:bold>\n                    <jats:sc>&lt;0.05)<\/jats:sc>\n                    by\n                    <jats:sc>l\u2010DOPA<\/jats:sc>\n                    and\n                    <jats:sc>l<\/jats:sc>\n                    \u2010leucine. The\n                    <jats:sc>\n                      [\n                      <jats:sup>14<\/jats:sup>\n                      C]\u2010l\u2010DOPA\n                    <\/jats:sc>\n                    outward transport was decreased 90% by LAT2 siRNA, but not by the mismatch LAT2 siRNA. However, treatment with the siRNA LAT2 did not affect the\n                    <jats:sc>l<\/jats:sc>\n                    \u2010DOPA\u2010induced fractional outflow of\n                    <jats:sc>\n                      [\n                      <jats:sup>14<\/jats:sup>\n                      C]\u2010l\u2010DOPA.\n                    <\/jats:sc>\n                    The Na\n                    <jats:sup>+<\/jats:sup>\n                    \u2010independent and pH\u2010sensitive\n                    <jats:sc>l\u2010DOPA<\/jats:sc>\n                    transporter may include the hetero amino acid exchanger LAT2, whose activation results in irans\u2010stimulation of\n                    <jats:sc>l\u2010DOPA<\/jats:sc>\n                    outward transfer.\u2014Soares\u2010da\u2010Silva, P., Serrao, M. P., Jo\u00e3o Pinho, M., Bonifacio, M.J. Cloning and gene silencing of LAT2, the L\u20103,4\u2010dihydroxyphenylalanine\n                    <jats:sc>(l\u2010DOPA)<\/jats:sc>\n                    transporter, in pig renal LLC\u2010PK\n                    <jats:sub>1<\/jats:sub>\n                    epithelial cells.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    18, 1489\u20131498 (2004)\n                  <\/jats:p>","DOI":"10.1096\/fj.04-1787com","type":"journal-article","created":{"date-parts":[[2004,10,12]],"date-time":"2004-10-12T22:32:47Z","timestamp":1097620367000},"page":"1489-1498","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Cloning and gene silencing of LAT2, the L\u20103,4\u2010dihydroxyphenylalanine\n                    <scp>(l\u2010DOPA)<\/scp>\n                    transporter, in pig renal LLC\u2010PK epithelial cells"],"prefix":"10.1096","volume":"18","author":[{"given":"PATR\u00cdCIO","family":"SOARES\u2010DA\u2010SILVA","sequence":"first","affiliation":[{"name":"Institute of Pharmacology and Therapeutics Faculty of Medicine Porto Portugal"}]},{"given":"MARIA PAULA","family":"SERR\u00c3O","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Therapeutics Faculty of Medicine Porto Portugal"}]},{"given":"MARIA JO\u00c3O","family":"PINKO","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Therapeutics Faculty of Medicine Porto Portugal"}]},{"given":"MARIA JO\u00c3O","family":"BONIF\u00c1CIO","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Therapeutics Faculty of Medicine Porto Portugal"}]}],"member":"311","published-online":{"date-parts":[[2004,10]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/00041552-200201000-00013"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11906-002-0013-6"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1177\/153537020322800202"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.57.6.889"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1291\/hypres.18.SupplementI_S179"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1474-8673.1990.tb00230.x"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.34.4.666"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.0000091822.00166.B1"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1081\/CEH-100100084"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.2174\/1389200013338324"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1999.0206"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.28.19745"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.2001.281.4.C1077"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.2000.279.4.F736"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/132.4.733"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.1986.tb04527.x"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(99)01387-6"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(00)02758-X"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.2001.280.2.C333"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.1975.tb04415.x"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02797469"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/35078107"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-6147(89)90266-6"},{"key":"e_1_2_6_25_1","volume-title":"Analyzing data with GraphPad prism","author":"Motulsky H. 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