{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,4,25]],"date-time":"2025-04-25T05:48:51Z","timestamp":1745560131689,"version":"3.37.3"},"reference-count":56,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2002,10,1]],"date-time":"2002-10-01T00:00:00Z","timestamp":1033430400000},"content-version":"vor","delay-in-days":273,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"FCT"},{"name":"POCTI"},{"DOI":"10.13039\/501100008530","name":"FEDER","doi-asserted-by":"crossref","award":["32550\/99"],"award-info":[{"award-number":["32550\/99"]}],"id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Cellular Biochemistry"],"published-print":{"date-parts":[[2002,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Alkaline phosphatase (ALP) refers to a group of nonspecific phosphomonoesterases located primarily in cell plasma membrane. It has been described in different cell lines that ecto\u2010ALP is directly or indirectly involved in the modulation of organic cation transport. We aimed to investigate, in Caco\u20102 cells, a putative modulation of 1\u2010methyl\u20104\u2010phenylpyridinium (MPP<jats:sup>+<\/jats:sup>) apical uptake by an ecto\u2010ALP activity. Ecto\u2010ALP activity and <jats:sup>3<\/jats:sup>H\u2010MPP<jats:sup>+<\/jats:sup> uptake were evaluated in intact Caco\u20102 cells (human colon adenocarcinoma cell line), in the absence and presence of a series of drugs. The activity of membrane\u2010bound ecto\u2010ALP expressed on the apical surface of Caco\u20102 cells was studied at physiological pH using <jats:italic>p<\/jats:italic>\u2010nitrophenylphosphate as substrate. The results showed that Caco\u20102 cells express ALP activity, characterized by an ecto\u2010oriented active site functional at physiological pH. Genistein (250 \u00b5M), 3\u2010isobutyl\u20101\u2010methylxanthine (1 mM), verapamil (100 \u00b5M), and ascorbic acid (1 mM) significantly increased ecto\u2010ALP activity and decreased <jats:sup>3<\/jats:sup>H\u2010MPP<jats:sup>+<\/jats:sup> apical transport in this cell line. Orthovanadate (100 \u00b5M) showed no effect on <jats:sup>3<\/jats:sup>H\u2010MPP<jats:sup>+<\/jats:sup> transport and on ecto\u2010ALP activity. On the other hand, okadaic acid (310 nM) and all <jats:italic>trans<\/jats:italic>\u2010retinoic acid (1 \u00b5M) significantly increased <jats:sup>3<\/jats:sup>H\u2010MPP<jats:sup>+<\/jats:sup> uptake and inhibited ecto\u2010ALP activity. There is a negative correlation between the effect of drugs upon ecto\u2010ALP activity and <jats:sup>3<\/jats:sup>H\u2010MPP<jats:sup>+<\/jats:sup> apical transport (<jats:italic>r<\/jats:italic>\u2009=\u2009\u22120.9; <jats:italic>P<\/jats:italic>\u2009=\u20090.0014). We suggest that apical uptake of organic cations in Caco\u20102 cells is affected by phosphorylation\/dephosphorylation mechanisms, and that ecto\u2010ALP activity may be involved in this process. J. Cell. Biochem. 87: 408\u2013416, 2002. \u00a9 2002 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jcb.10306","type":"journal-article","created":{"date-parts":[[2002,11,22]],"date-time":"2002-11-22T15:29:21Z","timestamp":1037978961000},"page":"408-416","source":"Crossref","is-referenced-by-count":11,"title":["Modulation of uptake of organic cationic drugs in cultured human colon adenocarcinoma Caco\u20102 cells by an ecto\u2010alkaline phosphatase activity"],"prefix":"10.1002","volume":"87","author":[{"given":"C.","family":"Calhau","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F.","family":"Martel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C.","family":"Hip\u00f3lito\u2010Reis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"I.","family":"Azevedo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2002,10,23]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4644(19960315)60:4<484::AID-JCB5>3.0.CO;2-O"},{"key":"e_1_2_6_3_1","first-page":"305","article-title":"Cell cultures as models for drug absorption across the intestinal mucosa","volume":"8","author":"Artursson P","year":"1991","journal-title":"Crit Rev Ther Drug Carrier Syst"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291X(91)91647-U"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004410051084"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(76)90527-3"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0009-9120(98)00094-0"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1159\/000016350"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0009-9120(00)00171-5"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.10027"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00210-002-0542-1"},{"key":"e_1_2_6_12_1","doi-asserted-by":"crossref","first-page":"7635","DOI":"10.1016\/S0021-9258(19)57445-2","article-title":"Dephosphorylation of phosphoproteins of human liver plasma membranes by endogenous and purified liver alkaline phosphatases","volume":"261","author":"Chan JRA","year":"1986","journal-title":"J Biol Chem"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.cb.08.110192.002335"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1615\/CritRevTherDrugCarrierSyst.v14.i3.20"},{"key":"e_1_2_6_15_1","first-page":"7111","article-title":"Ecto\u2010enzymes of the guinea pig polymorphonuclear leucocyte I. 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