Drug Transporters. Группа авторов

[6] K _m = 0.11 ± 0.01 mM V _max = 1.15 ± 0.09 nmol/mg protein/2 min [27] N‐methyl nicotinamide (NMN) hMATE1 K _m = 301 ± 18 μM [102] hMATE2‐K K _m = 422 ± 63 μM [102] Tetraethylammonium (TEA) hMATE1 K _m = 0.38 ± 0.07 mM V _max = 2.37 ± 0.23 nmol/mg protein/2 min [27] K _m = 0.58 ± 0.12 mM V _max = 0.81 ± 0.09 nmol/mg protein/min [67] K _m = 366 ± 17 μM V _max = 7.54 ± 0.21 nmol/min/mg protein [29] hMATE2‐K K _m = 0.83 ± 0.15 mM [6] K _m = 0.76 ± 0.18 mM V _max = 1.76 ± 0.25 nmol/mg protein/2 min [27] K _m = 375 ± 68 μM V _max = 1.16 ± 0.14 nmol/min/mg protein [29] rMate1 K _m = 570 ± 64 μM [16] K _m = 260 ± 10 μM V _max = 5.4 ± 0.2 nmol/min/mg protein [17] rbMate1 K _t = 160 ± 15 μM [20] rbMate2‐K K _t = 77 ± 12 μM [20] mMate2 K _m = 710 μM V _max = 400 pmol/min/mg protein [22]

      ^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