title: The anti-epileptic drug substance vigabatrin inhibits taurine transport in intestinal and renal cell culture models.
abstract: The GABA-mimetic anti-epileptic drug substance vigabatrin is used against infantile spasms. In vitro and in vivo experiments have shown that vigabatrin is transported via the proton coupled amino acid transporter (PAT1) mediating at least parts of the intestinal absorption of the drug. However, such evidence does not preclude the involvement of other transporters. The aim of the present study was, therefore, to investigate if vigabatrin interacts with taurine transport. The uptake of taurine was measured in intestinal human Caco-2 and canine MDCK cell monolayers in the absence or presence of amino acids such as GABA and vigabatrin. Vigabatrin inhibits the uptake of taurine in Caco-2 and MDCK cells to 34 ± 3 and 53 ± 2%, respectively, at a concentration of 30 mM. In Caco-2 cells the uptake of vigabatrin under neutral pH conditions is concentration-dependent and saturable with a Km-value of 27 mM (log Km is 1.43 ± 0.09). In conclusion, the present study shows that vigabatrin was able to inhibit the uptake of taurine in intestinal and renal cell culture models. Furthermore, uptake of vigabatrin in Caco-2 cells under neutral pH conditions was concentration-dependent and saturable and suggesting that vigabatrin partly was transported via a taurine transporter, which is likely to be TauT.
authors: Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark.
authors: Jakob
authors: J
authors: Plum
authors: Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark.
authors: Martha Kampp
authors: MK
authors: Nøhr
authors: Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark.
authors: Steen H
authors: SH
authors: Hansen
authors: Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark; Biologics and Pharmaceutical Science, H. Lundbeck A/S, DK-2500 Valby, Denmark.
authors: René
authors: R
authors: Holm
authors: Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark. Electronic address: carsten.uhdnielsen@sund.ku.dk.
authors: Carsten Uhd
authors: CU
authors: Nielsen
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D018938:Caco-2 Cells; D004285:Dogs; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism*; D061985:Madin Darby Canine Kidney Cells; D013654:Taurine / Q000378:metabolism*; D020888:Vigabatrin / Q000494:pharmacology*
chemical_list: D000927:Anticonvulsants; D013654:Taurine; D020888:Vigabatrin
keywords: Caco-2 cells; MDCK cells; PAT1; TauT; Taurine; Vigabatrin