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Third-party-funded project

Title:
Substrate recognition of a polyspecific cation transporter

Project management at the University of Würzburg:

• Prof. Dr. Hermann Koepsell

Participating scientists:

• Dr. Valentin Gorboulev
• Dr. Christopher Volk

Abstract:
In this research project we investigate the function, localization and
structure of polyspecific organic cation transporters. 1994 we cloned the first
organic cation transporter OCT1 that turned out to be the first member of
the large transporter family SLC22. This family also includes organic anion
transporters and transporters for zwitterions. After cloning of some organic
cation transporters from human and rat we investigated the function of these
transporters after expression in Xenopus oocytes and epithelial cell lines.
In addition we investigated the tissue and cellular distribution of these
transporters in liver and kidney. Furthermore we started a mutagenesis analysis
in order to map the substrate binding site. In collaboration with other research
groups we investigated the physiological role of organic cation transporters
with the help of transgenic animals.

Key words:
    Cation transporter

Projekt period: from 01.2000 to 12.2002

Funding institution:
DFG ,Granting date: 22.11.1999

Preceding project:
SFB 176 Teilprojekt A 22

Publications:

• Gorboulev V, Volk C, Arndt P, Akhoundova A, Koepsell H,. (1999). Selectivity of the polyspecific cation transporter rOCT1 is changed by mutation of aspartate 475 to glutamate. (monograph)
• Koepsell H, Gorboulev V, Arndt P,. (1999). Molecular pharmacology of organic cation transporters in kidney. (monograph)
• Koepsell H, Gorboulev V, Volk C, Karbach U,. (1999). Organic cation transporters in the kidney. (monograph)
• Budiman T, Bamberg E, Koepsell H, Nagel G. (2000). Mechanism of electrogenic cation transport by the cloned organic cation transporter 2 from rat. (monograph)
• Karbach U, Kricke J, Meyer-Wentrup F, Gorboulev V, Volk C, Loffing-Cueni D, Kaissling B, Bachmann S, Koepsell H. (2000). Localization of organic cation transporters OCT1 and OCT2 in rat kidney. (monograph)
• Koepsell H, Gorboulev V, Karbach U, Arndt P,. (2000). Polyspecific cation transporters in the proximal tubule. (monograph)
• Mehrens T, Lelleck S, Cetinkaya I, Knollmann M, Hohage H, Gorboulev V, Boknik P, Koepsell H, Schlatter E. (2000). The affinity of the organic cation transporter rOCT1 is increased by protein kinase C-dependent phosphorylation. (monograph)
• Arndt P, Volk C, Gorboulev V, Budiman T, Popp C, Ulzheimer-Teuber I, Akhoundova A, Koppatz S, Bamberg E, Nagel G, Koepsell H. (2001). Interaction of cations, anions, and weak base quinine with rat renal cation transporter rOCT2 compared with rOCT1. (monograph)
• Chen JJ, Li Z, Pan H, Murphy DL, Tamir H, Koepsell H, Gershon MD. (2001). Maintenance of serotonin in the intestinal mucosa and ganglia of mice that lack the high-affinity serotonin transporter: Abnormal intestinal motility and the expression of cation transporters. (monograph)
• Jonker JW, Wagenaar E, Mol CA, Buitelaar M, Koepsell H, Smit JW, Schinkel AH. (2001). Reduced hepatic uptake and intestinal excretion of organic cations in mice with a targeted disruption of the organic cation transporter 1 (oct1{Slc22a1}) gene. (monograph)
• Koepsell H, Gorboulev V, Popp C, van Montfoort JE, Meier PJ, Arndt P, Volk C,. (2001). Organic cation transporters in the sinusoidal membrane of hepatocytes (2001) In: Matern S, Boyer JL,Keppler D, Meier-Abt PJ (eds) Hepatobiliary Transport: From Bench to Bedside.. (monograph)
• Van Montfoort JE, Müller M, Groothuis GM, Meijer DK, Koepsell H, Meier PJ. (2001). Comparison of. (monograph)