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2016 ; 17
(8
): ä Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
Urinary Dopamine as a Potential Index of the Transport Activity of Multidrug and
Toxin Extrusion in the Kidney
#MMPMID27483254
Kajiwara M
; Ban T
; Matsubara K
; Nakanishi Y
; Masuda S
Int J Mol Sci
2016[Jul]; 17
(8
): ä PMID27483254
show ga
Dopamine is a cationic natriuretic catecholamine synthesized in proximal tubular
cells (PTCs) of the kidney before secretion into the lumen, a key site of its
action. However, the molecular mechanisms underlying dopamine secretion into the
lumen remain unclear. Multidrug and toxin extrusion (MATE) is a H?/organic cation
antiporter that is highly expressed in the brush border membrane of PTCs and
mediates the efflux of organic cations, including metformin and cisplatin, from
the epithelial cells into the urine. Therefore, we hypothesized that MATE
mediates dopamine secretion, a cationic catecholamine, into the tubule lumen,
thereby regulating natriuresis. Here, we show that [³H]dopamine uptake in human
(h) MATE1-, hMATE-2K- and mouse (m) MATE-expressing cells exhibited saturable
kinetics. Fluid retention and decreased urinary excretion of dopamine and Na?
were observed in Mate1-knockout mice compared to that in wild-type mice.
Imatinib, a MATE inhibitor, inhibited [³H]dopamine uptake by hMATE1-, hMATE2-K-
and mMATE1-expressing cells in a concentration-dependent manner. At
clinically-relevant concentrations, imatinib inhibited [³H]dopamine uptake by
hMATE1- and hMATE2-K-expressing cells. The urinary excretion of dopamine and Na?
decreased and fluid retention occurred in imatinib-treated mice. In conclusion,
MATE transporters secrete renally-synthesized dopamine, and therefore, urinary
dopamine has the potential to be an index of the MATE transporter activity.
|Animals
[MESH]
|Biological Transport
[MESH]
|Biomarkers/*urine
[MESH]
|Chromatography, Liquid
[MESH]
|Dopamine/pharmacokinetics/*urine
[MESH]
|HEK293 Cells
[MESH]
|Humans
[MESH]
|Imatinib Mesylate/pharmacology
[MESH]
|Immunoenzyme Techniques
[MESH]
|Kidney/drug effects/*metabolism
[MESH]
|Male
[MESH]
|Mice
[MESH]
|Mice, Inbred C57BL
[MESH]
|Mice, Knockout
[MESH]
|Organic Cation Transport Proteins/*physiology
[MESH]