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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Curr+Opin+Nephrol+Hypertens
2016 ; 25
(5
): 444-51
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Urea transport and clinical potential of urearetics
#MMPMID27367911
Klein JD
; Sands JM
Curr Opin Nephrol Hypertens
2016[Sep]; 25
(5
): 444-51
PMID27367911
show ga
PURPOSE OF REVIEW: Urea is transported by urea transporter proteins in kidney,
erythrocytes, and other tissues. Mice in which different urea transporters have
been knocked out have urine-concentrating defects, which has led to the
development and testing of urea transporters Slc14A2 (UT-A) and Slc14A1 (UT-B)
inhibitors as urearetics. This review summarizes the knowledge gained during the
past year on urea transporter regulation and investigations into the clinical
potential of urearetics. RECENT FINDINGS: UT-A1 undergoes several
posttranslational modifications that increase its function by increasing UT-A1
accumulation in the apical plasma membrane. UT-A1 is phosphorylated by protein
kinase A, exchange protein activated by cyclic AMP, protein kinase C?, and
AMP-activated protein kinase, all at different serine residues. UT-A1 is also
regulated by 14-3-3, which contributes to UT-A1 removal from the membrane. UT-A1
is glycosylated with various glycan moieties in animal models of diabetes
mellitus. Transgenic expression of UT-A1 into UT-A1/UT-A3 knockout mice restores
urine-concentrating ability. UT-B is present in descending vasa recta and urinary
bladder, and is linked to bladder cancer. Inhibitors of UT-A and UT-B have been
developed that result in diuresis with fewer abnormalities in serum electrolytes
than conventional diuretics. SUMMARY: Urea transporters play critical roles in
the urine-concentrating mechanism. Urea transport inhibitors are a promising new
class of diuretic agent.
|*Biological Transport/drug effects
[MESH]
|Animals
[MESH]
|Cyclic AMP-Dependent Protein Kinases/metabolism
[MESH]
|Diuresis
[MESH]
|Diuretics/pharmacology
[MESH]
|Glycosylation
[MESH]
|Humans
[MESH]
|Kidney/*metabolism
[MESH]
|Membrane Transport Proteins/genetics/*metabolism
[MESH]
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