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3.3.2.6 Endogenous Molecules
ОглавлениеEndogenous molecules have been identified as substrates of MATE/Mate transporters. For example, the initial development of Mate1 knockout mice confirmed the in vitro evidence that this transporter can efflux creatinine. Baseline levels of creatinine within the blood of Mate1 knockout mice are elevated [32]. N 1‐methyladenosine, which is a metabolite of niacin or nicotinamide, is a substrate of MATE2‐K in vitro [50]. Treatment of mice with a Mate inhibitor increased plasma concentrations of N 1‐methyladenosine in a time‐dependent manner and reduced its overall renal clearance [50]. The cationic neurotransmitter dopamine is also a substrate of hMATE1, hMATE2‐K, and mMate1 in vitro. in vivo, mice lacking mMate1 have reduced urinary excretion of dopamine. Moreover, the ability of renally synthesized dopamine to cause natriuresis and diuresis is absent in Mate1 knockout mice [51]. These data may be relevant for identifying endogenous biomarkers of OCT/MATE function in drug interaction and pharmacogenetic studies (see below).