{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T22:24:58Z","timestamp":1792189498906,"version":"4.4.0"},"reference-count":65,"publisher":"American Physiological Society","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Cell Physiology"],"published-print":{"date-parts":[[2009,3]]},"abstract":"<jats:p>Organic anion transporting polypeptides (humans OATPs, rodents Oatps) are expressed in most mammalian tissues and mediate cellular uptake of a wide variety of amphipathic organic compounds such as bile salts, steroid conjugates, oligopeptides, and a large list of drugs, probably by acting as anion exchangers. In the present study we aimed to investigate the role of the extracellular pH on the transport activity of nine human and four rat OATPs\/Oatps. Furthermore, we aimed to test the concept that OATP\/Oatp transport activity is accompanied by extrusion of bicarbonate. By using amphibian Xenopus laevis oocytes expressing OATPs\/Oatps and mammalian cell lines stably transfected with OATPs\/Oatps, we could demonstrate that in all OATPs\/Oatps investigated, with the exception of OATP1C1, a low extracellular pH stimulated transport activity. This stimulation was accompanied by an increased substrate affinity as evidenced by lower apparent Michaelis-Menten constant values. OATP1C1 is lacking a highly conserved histidine in the third transmembrane domain, which was shown by site-directed mutagenesis to be critically involved in the pH dependency of OATPs\/Oatps. Using online intracellular pH measurements in OATP\/Oatp-transfected Chinese Hamster Ovary (CHO)-K1 cells, we could demonstrate the presence of a 4,4\u2032-diisothiocyanatostilbene-2,2\u2032-disulfonic acid-sensitive chloride\/bicarbonate exchanger in CHO-K1 cells and that OATP\/Oatp-mediated substrate transport is paralleled by bicarbonate efflux. We conclude that the pH dependency of OATPs\/Oatps may lead to a stimulation of substrate transport in an acidic microenvironment and that the OATP\/Oatp-mediated substrate transport into cells is generally compensated or accompanied by bicarbonate efflux.<\/jats:p>","DOI":"10.1152\/ajpcell.00436.2008","type":"journal-article","created":{"date-parts":[[2009,1,8]],"date-time":"2009-01-08T02:36:20Z","timestamp":1231382180000},"page":"C570-C582","source":"Crossref","is-referenced-by-count":171,"title":["Mechanisms of pH-gradient driven transport mediated by organic anion polypeptide transporters"],"prefix":"10.1152","volume":"296","author":[{"given":"Simone","family":"Leuthold","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"Hagenbuch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nilufar","family":"Mohebbi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carsten A.","family":"Wagner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter J.","family":"Meier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"Stieger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"R1","doi-asserted-by":"crossref","unstructured":"Asaka J, Terada T, Tsuda M, Katsura T, Inui K.Identification of essential 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glutathione as a driving force and leukotriene C4 as a substrate for oatp1, the hepatic sinusoidal organic solute transporter.J Biol Chem273: 16184\u201316191, 1998.","DOI":"10.1074\/jbc.273.26.16184"},{"key":"R33","doi-asserted-by":"crossref","unstructured":"Li L, Meier PJ, Ballatori N.Oatp2 mediates bidirectional organic solute transport: a role for intracellular glutathione.Mol Pharmacol58: 335\u2013340, 2000.","DOI":"10.1124\/mol.58.2.335"},{"key":"R34","doi-asserted-by":"crossref","unstructured":"Marin JJ, Mangas D, Martinez-Diez MC, El-Mir MY, Briz O, Serrano MA.Sensitivity of bile acid transport by organic anion-transporting polypeptides to intracellular pH.Biochim Biophys Acta1611: 249\u2013257, 2003.","DOI":"10.1016\/S0005-2736(03)00080-4"},{"key":"R35","doi-asserted-by":"crossref","unstructured":"Meier-Abt F, Faulstich H, Hagenbuch B.Identification of phalloidin uptake systems of rat and human liver.Biochim Biophys Acta1664: 64\u201369, 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