Drug Transporters. Группа авторов

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	hMATE1	K m = 0.20 ± 0.03 mM V max = 0.70 ± 0.05 nmol/mg protein/min	[132]
	hMATE2‐K	K m = 0.20 ± 0.03 mM V max = 3.0 ± 0.2 nmol/mg protein/min	[132]
(R,R)‐Fenoterol	MATE1	K m = 111.3 ± 16.3 μM V max = 2091.3 ± 133.7 pmol/mg protein/min	[41]
	MATE2‐K	K m = 76.4 ± 4.1 μM V max = 728.6 ± 92.9 pmol/mg protein/min	[41]
(S,S)‐Fenoterol	MATE1	K m = 103.5 ± 18.0 μM V max = 1822.3 ± 360.6 pmol/mg protein/min	[41]
	MATE2‐K	K m = 69.5 ± 1.1 μM V max = 511.7 ± 47.0 pmol/mg protein/min	[41]
(R,R)‐Formoterol	MATE1	K m = 231.5 ± 114.7 μM V max = 301.5 ± 152.3 pmol/mg protein/min	[41]
	MATE2‐K	K m = 181.7 ± 158.1 μM V max = 77.6 ± 38.5 pmol/mg protein/min	[41]
(S,S)‐Formoterol	MATE1	K m = 343.8 ± 321.0 μM V max = 447.3 ± 363.4 pmol/mg protein/min	[41]
	MATE2‐K	K m = 35.7 ± 12.5 μM V max = 33.7 ± 6.1 pmol/mg protein/min	[41]
Ganciclovir	hMATE1	K m = 5.12 ± 0.27 mM V max = 2.12 ± 0.25 nmol/mg protein/2 min	[27]
	hMATE2‐K	K m = 4.28 ± 0.61 mM V max = 1.61 ± 0.27 nmol/mg protein/2 min	[27]
Ipratropium	MATE1	K m = 44.8 ± 2.9 μM V max = 3342.7 ± 183.6 pmol/mg protein/min	[44]
	MATE2‐K	K m = 95.7 ± 7.5 μM V Скачать книгу В начало < 33 34 35 36 37 38 39 40 41 42 > В конец e-mail: [email protected]