title: Inhibitory action of antidepressants on mouse Betaine/GABA transporter (BGT1) heterologously expressed in cell cultures.
abstract: Betaine/γ-aminobutyric acid (GABA) transporter (BGT1, SLC6A12) is a member of the Na(+)- and Cl(-)-dependent neurotransmitter transporter gene family with a homology to the GABA transporters (GATs), GAT1 (SLC6A1), GAT2 (SLC6A13) and GAT3 (SLC6A11) (HUGO nomenclature). Since antidepressants have been reported to inhibit GABA uptake, we examined those effects on mouse BGT1 (mBGT1) in comparison with other mouse GAT (mGAT) subtypes in the heterologously expressed cell cultures. All antidepressants tested here inhibited the [(3)H]GABA uptake through mBGT1 and mGATs in a rank order of potency with mBGT1 > mGAT1-3. Kinetic analyses for maprotilline, mianserine and trimipramine revealed that they inhibited mBGT1 and mGAT1 noncompetitively, except that mianserine competitively inhibited mBGT1. These results provided a clue to investigate the structure-function relationship of mBGT1 using antidepressants as a tool, leading to the identification of potential candidates for selective and specific inhibitors of mBGT1.
authors.affiliation: Department of Dental Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8525, Japan.
authors.lastname: Gerile
authors.affiliation: Department of Dental Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8525, Japan.
authors.forename: Chiharu
authors.identifier: 0000-0002-5606-0710
authors.initials: C
authors.lastname: Sogawa
authors.affiliation: RI Research Center, Okayama University Dental School, Okayama 700-8525, Japan.
authors.forename: Kazumi
authors.initials: K
authors.lastname: Ohyama
authors.affiliation: Laboratory of Physiology and Anatomy, College of Pharmacy, Nihon University,Funabashi 274-8555, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Masuko
authors.affiliation: Laboratory of Physiology and Anatomy, College of Pharmacy, Nihon University,Funabashi 274-8555, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Kusama
authors.affiliation: Department of Dental Pharmacology, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima 734-8553, Japan.
authors.forename: Katsuya
authors.initials: K
authors.lastname: Morita
authors.affiliation: Department of Dental Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8525, Japan.
authors.forename: Norio
authors.initials: N
authors.lastname: Sogawa
authors.affiliation: Department of Dental Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8525, Japan.
authors.forename: Shigeo
authors.initials: S
authors.lastname: Kitayama
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects; D019556:COS Cells; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D050485:GABA Plasma Membrane Transport Proteins / Q000096:biosynthesis / Q000378:metabolism*; D007700:Kinetics; D051379:Mice; D051381:Rats; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D000928:Antidepressive Agents; D050485:GABA Plasma Membrane Transport Proteins; D050486:Serotonin Plasma Membrane Transport Proteins; C490439:Slc6a12 protein, mouse; D005680:gamma-Aminobutyric Acid