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Drug Transporters. Группа авторов
Читать онлайн.Название Drug Transporters
Год выпуска 0
isbn 9781119739876
Автор произведения Группа авторов
Жанр Медицина
Издательство John Wiley & Sons Limited
a N.R.: not reported.
Through the use of double‐transfected cells expressing both hOCT1 and hOCT2 along with hMATE1, it is possible to investigate the role of hMATE1 in the apical efflux of chemicals [30]. In MDCK cells expressing both hOCT1/hMATE1, the transcellular transport (basolateral‐to‐apical) can be observed for TEA, MPP+, metformin, cimetidine, creatinine, guanidine, procainamide, and quinidine [31]. Largely similar results have been obtained for polarized MDCK cells containing hOCT2/hMATE1 [30, 31].
3.3.2.1 Metformin
The diabetic drug metformin is a classic substrate of MATE transporters. Deletion of mMate1 expression significantly increases concentrations of metformin in plasma, kidneys, and liver while reducing urinary excretion in mice [32, 33]. These data were confirmed by positron emission tomography using [11C]metformin [34, 35]. Pharmacological inhibition of Mate transporters prolonged hepatic and renal accumulation of [11C]metformin [35]. One of the notable side effects of metformin pharmacotherapy is lactic acidosis. Compared with wild‐type mice, mice lacking mMate1 expression exhibit higher blood lactate levels after metformin treatment [36].
TABLE 3.2 Drug and metabolite substrates of MATE transporters
Substrates | Isoforms | Transport kinetics | References |
---|---|---|---|
Acyclovir | hMATE1 | K m = 2.64 ± 0.40 mM V max = 1.24 ± 0.24 nmol/mg protein/2 min | [27] |
hMATE2‐K | K m = 4.32 ± 0.44 mM V max = 1.89 ± 0.15 nmol/mg protein/2 min | [27] | |
Atenolol | hMATE1 | K m = 32 ± 5 μM V max = 323 ± 12 pmol/min/mg protein | [43] |
hMATE2‐K | K m = 76 ± 14 μM V max = 500 ± 22 pmol/min/mg protein | [43] | |
Cephalexin | hMATE1 | K m = 5.9 ± 0.5 mM V max = 12.6 ± 1.1 nmol/mg protein/min | [28] |
Cimetidine | hMATE1 | K m = 0.17 ± 0.02 mM V max = 0.27 ± 0.03 nmol/mg protein/2 min | [27] |
K m = 7.4 ± 1.2 μM V max = 103.9 ± 6.5 pmol/mg protein/min | [67] | ||
K m = 8.00 ± 0.26 μM V max = 0.167 ± 0.020 nmol/min/mg protein | [29] | ||
hMATE2‐K | K m = 0.37 ± 0.14 mM | [6] | |
K m = 0.12 ± 0.04 mM V max = 0.23 ± 0.05 nmol/mg protein/2 min | [27] | ||
K m = 18.18 ± 0.69 μM V max = 0.216 ± 0.018 nmol/min/mg protein | [29] | ||
rMATE1 | K m = 3.01 ± 0.21 μM V max = 87.9 ± 3.7 pmol/min/mg protein | [17] | |
Cycloguanil | MATE1 | V max = 40 ± 9 pmol/mg protein/min | [130] |
MATE2‐K | V max = 56 ± 15 pmol/mg protein/min | [130] | |
Dabigatran | hMATE1 | K m = 4.0 ± 0.9 μM V max = 12.1 ± 0.9 pmol/mg protein/1.5 min | [131] |
hMATE2‐K | K m = 8.0 ± 0.8 μM V max = 84.3 ± 5.4 pmol/mg protein/1.5 min | [131] | |
Entecavir
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