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Drug
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Compound
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Query: UNIPROT:P41181 (
collecting duct
)
5,183
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
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.
...
PMID:Probenecid Pre-treatment Downregulates the Kidney Cl
-
/HCO
3
-
Exchanger (Pendrin) and Potentiates Hydrochlorothiazide-Induced Diuresis. 3005 Apr 51
Aldosterone-sensitive distal nephron (ASDN) including the distal convoluted tubule (DCT), connecting tubule (CNT) and
collecting duct
(CD) plays an important role in the regulation of hormone-dependent Na
+
reabsorption and dietary K
+
-intake dependent K
+
excretion. The major Na
+
transporters in the ASDN are
thiazide-sensitive Na-Cl cotransporter
(NCC), epithelial Na
+
channel (ENaC), pendrin/Na
+
-dependent Cl
-
-bicarbonate exchanger (NDCBE). Whereas major K
+
channels in the ASDN are Kir4.1 and Kir5.1 in the basolateral membrane; and Kir1.1 (ROMK) and Ca
2+
activated big conductance K
+
channel (BK) in the apical membrane. Although a variety of in vitro cell lines of the ASDN is available and these cell models have been employed for studying Na
+
and K
+
channels, the biophysical properties and the regulation of Na
+
and K
+
channels in vitro cell models may not be able to recapitulate those in vivo conditions. Thus, the studies performed in the native ASDN are essential for providing highly physiological relevant information and for understanding the Na
+
and K
+
transport in the ASDN. Here we provide a detailed methodology describing how to perform the electrophysiological measurement in the native DCT, CNT and cortical
collecting duct
(
CCD
).
...
PMID:Studying Na
+
and K
+
channels in aldosterone-sensitive distal nephrons. 3139 77
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