Inhibitory action of antidepressants on mouse betaine/GABA transporter (BGT1) heterologously expressed in cell cultures

Gerile; Chiharu Sogawa; Kazumi Ohyama; Takashi Masuko; Tadashi Kusama; Katsuya Morita; Norio Sogawa; Shigeo Kitayama

doi:10.3390/ijms13032578

Inhibitory action of antidepressants on mouse betaine/GABA transporter (BGT1) heterologously expressed in cell cultures

Gerile, Chiharu Sogawa, Kazumi Ohyama, Takashi Masuko, Tadashi Kusama, Katsuya Morita, Norio Sogawa, Shigeo Kitayama

Research output: Contribution to journal › Article › peer-review

8 Citations (Scopus)

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 [ ³H]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.

Original language	English
Pages (from-to)	2578-2589
Number of pages	12
Journal	International journal of molecular sciences
Volume	13
Issue number	3
DOIs	https://doi.org/10.3390/ijms13032578
Publication status	Published - Mar 2012
Externally published	Yes

Keywords

Antidepressant
Betaine
GABA
Transporter
Uptake inhibitor

ASJC Scopus subject areas

Catalysis
Molecular Biology
Spectroscopy
Computer Science Applications
Physical and Theoretical Chemistry
Organic Chemistry
Inorganic Chemistry

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10.3390/ijms13032578

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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 [ 3H]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.",

keywords = "Antidepressant, Betaine, GABA, Transporter, Uptake inhibitor",

author = "Gerile and Chiharu Sogawa and Kazumi Ohyama and Takashi Masuko and Tadashi Kusama and Katsuya Morita and Norio Sogawa and Shigeo Kitayama",

year = "2012",

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AU - Gerile,

AU - Sogawa, Chiharu

AU - Ohyama, Kazumi

AU - Masuko, Takashi

AU - Kusama, Tadashi

AU - Morita, Katsuya

AU - Sogawa, Norio

AU - Kitayama, Shigeo

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N2 - 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 [ 3H]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.

AB - 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 [ 3H]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.

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KW - Betaine

KW - GABA

KW - Transporter

KW - Uptake inhibitor

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Inhibitory action of antidepressants on mouse betaine/GABA transporter (BGT1) heterologously expressed in cell cultures

Abstract

Keywords

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