QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: dmd.104.001560v1 33/1/31    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Grube, M. Articles by Kroemer, H. K. Search for Related Content PubMed PubMed Citation Articles by Grube, M. Articles by Kroemer, H. K.

EXPRESSION, LOCALIZATION, AND FUNCTION OF THE CARNITINE TRANSPORTER OCTN2 (SLC22A5) IN HUMAN PLACENTA

Peter Holtz Research Center of Pharmacology and Experimental Therapeutics, Department of Pharmacology (M.G., H.M.z.S., K.D., D.P., K.-U.M., G.J., H.K.K.) and Department of Neonatology (K.L., C.F.), Ernst Moritz Arndt University, Greifswald, Germany

L-carnitine is assumed to play an important role in fetal development, and there is evidence that carnitine is transported across the placenta. The protein involved in this transfer, however, has not been identified on a molecular level. We therefore characterized localization and function of the carnitine transporter OCTN2 in human placenta. Significant expression of OCTN2 mRNA was detected in human placenta applying real-time polymerase chain reaction technology. Confocal immunofluorescence microscopy using an antibody directed against the carboxy terminus of OCTN2 protein revealed that it is predominantly expressed in the apical membrane of syncytiotrophoblasts. This was confirmed by the costaining of organic anion-transporting polypeptide B and MRP2, which are known to be expressed mainly in the basal and apical syncytiotrophoblasts membrane, respectively. To further support this finding, we performed transport studies using basal and apical placenta membrane vesicles. We could demonstrate that the carnitine uptake into the apical vesicles was about eight times higher compared with the basal ones. Moreover, this uptake was sodium- and pH-dependent with an apparent K_m value of 21 µM and inhibited by verapamil, which is in line with published data for recombinant OCTN2. Finally, experiments using trophoblasts in cell culture revealed that expression of OCTN2 paralleled human choriogonadotropin production and thus is modulated by cellular differentiation. In summary, we show expression and function of OCTN2 in human placenta. Moreover, several lines of evidence indicate that OCTN2 is localized in the apical membrane of syncytiotrophoblasts, thereby suggesting a major role in the uptake of carnitine during fetal development.

This article has been cited by other articles:

				T. Kano, Y. Kato, K. Ito, T. Ogihara, Y. Kubo, and A. Tsuji Carnitine/Organic Cation Transporter OCTN2 (Slc22a5) Is Responsible for Renal Secretion of Cephaloridine in Mice Drug Metab. Dispos., May 1, 2009; 37(5): 1009 - 1016. [Abstract] [Full Text] [PDF]

				Q. Garrett, S. Xu, P. A. Simmons, J. Vehige, J. L. Flanagan, and M. D. Willcox Expression and Localization of Carnitine/Organic Cation Transporter OCTN1 and OCTN2 in Ocular Epithelium Invest. Ophthalmol. Vis. Sci., November 1, 2008; 49(11): 4844 - 4849. [Abstract] [Full Text] [PDF]

				M. Grube, S. Reuther, H. Meyer zu Schwabedissen, K. Kock, K. Draber, C. A. Ritter, C. Fusch, G. Jedlitschky, and H. K. Kroemer Organic Anion Transporting Polypeptide 2B1 and Breast Cancer Resistance Protein Interact in the Transepithelial Transport of Steroid Sulfates in Human Placenta Drug Metab. Dispos., January 1, 2007; 35(1): 30 - 35. [Abstract] [Full Text] [PDF]

				G. Horvath, N. Schmid, M. A. Fragoso, A. Schmid, G. E. Conner, M. Salathe, and A. Wanner Epithelial Organic Cation Transporters Ensure pH-Dependent Drug Absorption in the Airway Am. J. Respir. Cell Mol. Biol., January 1, 2007; 36(1): 53 - 60. [Abstract] [Full Text] [PDF]

				M. Grube, K. Kock, S. Karner, S. Reuther, C. A. Ritter, G. Jedlitschky, and H. K. Kroemer Modification of OATP2B1-Mediated Transport by Steroid Hormones Mol. Pharmacol., November 1, 2006; 70(5): 1735 - 1741. [Abstract] [Full Text] [PDF]

				M. Grube, H. E.U. Meyer zu Schwabedissen, D. Prager;, J. Haney, K.-U. Moritz, K. Meissner, D. Rosskopf, L. Eckel, M. Bohm, G. Jedlitschky, et al. Uptake of Cardiovascular Drugs Into the Human Heart: Expression, Regulation, and Function of the Carnitine Transporter OCTN2 (SLC22A5) Circulation, February 28, 2006; 113(8): 1114 - 1122. [Abstract] [Full Text] [PDF]