Vectorial transport of the arginine derivatives asymmetric dimethylarginine (ADMA) andl-homoarginine by OATP4C1 and P-glycoprotein studied in double-transfected MDCK cells

Taghikhani EP, Maas R, Taudte V, Geßner A, Fromm M, König J (2020)

Publication Type: Journal article

Publication year: 2020

Journal

Abstract

Elevated plasma concentrations of the uremic toxin asymmetric dimethylarginine (ADMA) and low plasma concentrations ofl-homoarginine are independently associated with cardiovascular events and mortality. Key enzymes involved in the homeostasis of both arginine derivatives are expressed in proximal tubule cells of the kidney. To get access to these enzymes, transport proteins are important. One of the transporters mediating the transport of ADMA andl-homoarginine is the solute carrier superfamily (SLC) member OATP4C1, located in the basolateral membrane of proximal tubule cells. To gain insights into the role of export pumps in the transport of both substances, we established a double-transfected MDCK cell line expressing OATP4C1 and the export pump P-glycoprotein (P-gp). Using MDCK cell monolayers, we demonstrated in time-dependent and concentration-dependent vectorial transport experiments that ADMA andl-homoarginine are transported from the basolateral to the apical compartment of MDCK-OATP4C1-P-gp cells with significantly higher transport rates compared to single-transfected MDCK-OATP4C1, MDCK-P-gp and MDCK-VC (control) cells (e.g. transport ratio MDCK-OATP4C1-P-gp/MDCK-VC: for 50 mu M ADMA = 2.0-fold, for 50 mu Ml-homoarginine = 3.4-fold). These results indicate that both OATP4C1 and P-gp transport the arginine derivatives ADMA andl-homoarginine and are, therefore, important for the homoeostasis of both substances.

Authors with CRIS profile

Emir Puyan Taghikhani Lehrstuhl für Klinische Pharmakologie und Klinische Toxikologie Renke Maas Professur für Arzneimitteltherapiesicherheit und Klinische Pharmakologie Verena Taudte Lehrstuhl für Klinische Pharmakologie und Klinische Toxikologie Arne Geßner Lehrstuhl für Klinische Pharmakologie und Klinische Toxikologie Martin Fromm Lehrstuhl für Klinische Pharmakologie und Klinische Toxikologie Jörg König Lehrstuhl für Klinische Pharmakologie und Klinische Toxikologie

How to cite

APA:

Taghikhani, E.P., Maas, R., Taudte, V., Geßner, A., Fromm, M., & König, J. (2020). Vectorial transport of the arginine derivatives asymmetric dimethylarginine (ADMA) andl-homoarginine by OATP4C1 and P-glycoprotein studied in double-transfected MDCK cells. Amino Acids. https://doi.org/10.1007/s00726-020-02867-8

MLA:

Taghikhani, Emir Puyan, et al. "Vectorial transport of the arginine derivatives asymmetric dimethylarginine (ADMA) andl-homoarginine by OATP4C1 and P-glycoprotein studied in double-transfected MDCK cells." Amino Acids (2020).

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