Deprecated: Implicit conversion from float 213.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 213.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 213.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 213.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 213.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 213.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 247.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 247.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 247.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\30050451
.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Front+Physiol
2018 ; 9
(ä): 849
Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
Probenecid Pre-treatment Downregulates the Kidney Cl(-)/HCO(3)(-) Exchanger
(Pendrin) and Potentiates Hydrochlorothiazide-Induced Diuresis
#MMPMID30050451
Barone S
; Xu J
; Zahedi K
; Brooks M
; Soleimani M
Front Physiol
2018[]; 9
(ä): 849
PMID30050451
show ga
Background: Probenecid is a uricosuric agent that in addition to exerting a
positive ionotropic effect in the heart, blocks the ATP transporter Pannexin 1
and inhibits the Cl(-)/HCO(3)(-) exchanger, pendrin. In the kidney, pendrin
blunts the loss of salt wasting secondary to the inhibition of the
thiazide-sensitive Na(+)-Cl(-) co-transporter (NCC/SLC12A3). Hypothesis:
Pre-treatment with probenecid down-regulates pendrin; therefore, leaving NCC as
the main salt absorbing transporter in the distal nephron, and hence enhances the
hydrochlorothiazide (HCTZ)-induced diuresis. Methods: Daily balance studies,
blood and urine chemical analysis, immunofluorescence, as well as western and
northern blot analyses were utilized to examine the effects of probenecid alone
(at 250 mg/kg/day) or in combination with HCTZ (at 40 mg/kg/day) on kidney
function and on salt and water transporters in the collecting duct. Results: Male
Sprague Dawley rats were subjected to three different protocols: (1) HCTZ for 4
days, (2) probenecid for 10 days, and (3) primed with probenecid for 6 days
followed by probenecid and HCTZ for 4 additional days. Treatment protocol 1 (HCTZ
for 4 days) only mildly increased the urine volume (U Vol) from a baseline of
9.8-13.4 ml/day. In response to treatment protocol 2 (probenecid for 10 days), U
Vol increased to 15.9 ml/24 h. Treatment protocol 3 (probenecid for 6 days
followed by probenecid and HCTZ for 4 additional days) increased the U Vol to
42.9 ml/day on day 4 of co-treatment with HCTZ and probenecid (compared to
probenecid p = 0.003, n = 5 or HCTZ alone p = 0.001, n = 5). Probenecid treatment
at 250 mg/kg/day downregulated the expression of pendrin and led to a decrease in
AQP2 expression. Enhanced diuresis by probenecid plus HCTZ was not associated
with volume depletion. Conclusion: Probenecid pre-treatment downregulates pendrin
and robustly enhances diuresis by HCTZ-mediated NCC inhibition in kidney.