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 | |
| Publication status | Published - Mar 2012 |
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Keywords
- Antidepressant
- Betaine
- GABA
- Transporter
- Uptake inhibitor
ASJC Scopus subject areas
- Computer Science Applications
- Molecular Biology
- Catalysis
- Inorganic Chemistry
- Spectroscopy
- Organic Chemistry
- Physical and Theoretical Chemistry
- Medicine(all)
Cite this
Inhibitory action of antidepressants on mouse betaine/GABA transporter (BGT1) heterologously expressed in cell cultures. / Gerile, ; Sogawa, Chiharu; Ohyama, Kazumi; Masuko, Takashi; Kusama, Tadashi; Morita, Katsuya; Sogawa, Norio; Kitayama, Shigeo.
In: International Journal of Molecular Sciences, Vol. 13, No. 3, 03.2012, p. 2578-2589.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Inhibitory action of antidepressants on mouse betaine/GABA transporter (BGT1) heterologously expressed in cell cultures
AU - Gerile,
AU - Sogawa, Chiharu
AU - Ohyama, Kazumi
AU - Masuko, Takashi
AU - Kusama, Tadashi
AU - Morita, Katsuya
AU - Sogawa, Norio
AU - Kitayama, Shigeo
PY - 2012/3
Y1 - 2012/3
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.
KW - Antidepressant
KW - Betaine
KW - GABA
KW - Transporter
KW - Uptake inhibitor
UR - http://www.scopus.com/inward/record.url?scp=84859083494&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84859083494&partnerID=8YFLogxK
U2 - 10.3390/ijms13032578
DO - 10.3390/ijms13032578
M3 - Article
C2 - 22489112
AN - SCOPUS:84859083494
VL - 13
SP - 2578
EP - 2589
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
SN - 1661-6596
IS - 3
ER -