Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P41181 (collecting duct)
 5,183 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Clinical disorders of extracellular fluid (ECF) volume regulation are often associated with changes in plasma urea concentration. To investigate possible renal causes, we measured the relative abundance of the urea transporters UT-A1, UT-A2, and UT-A3 in renal medulla of rats with aldosterone-induced NaCl retention. ECF volume-expanded rats received aldosterone by osmotic minipump plus a diet containing a high level of NaCl. Control rats received the same infusion of aldosterone plus a virtually NaCl-free diet, which prevented ECF volume expansion. Preliminary measurements demonstrated transient positive Na and water balance, decreased serum urea concentration, and increased urea clearance, but no change in creatinine clearance. Immunoblotting of homogenates from inner medulla showed a marked decrease in the abundance of the collecting duct urea transporters UT-A1 and UT-A3. There were no differences in the abundance of UT-A2, aquaporin (AQP)-2, AQP-3, or AQP-4 in ECF volume-expanded rats vs. controls. Time course experiments demonstrated that changes in UT-A1 abundance paralleled the fall in serum urea concentration after the switch from a low-NaCl to a high-NaCl diet, whereas the fall in UT-A3 abundance was delayed. Candesartan administration markedly decreased the abundance of UT-A1 and UT-A3 in the renal inner medulla, which is consistent with a role for the angiotensin II type 1 receptor in urea transport regulation. The results support the view that ECF-related changes in serum urea concentration are mediated, at least in part, through altered urea transporter abundance.
 ...
PMID:Decreased abundance of collecting duct urea transporters UT-A1 and UT-A3 with ECF volume expansion. 1188 Mar 17

We carried out semiquantitative immunoblotting of kidney to identify apical sodium transporter proteins whose abundances are regulated by angiotensin II. In NaCl-restricted rats (0.5 mEq Na/200 g BW/d), the type 1 angiotensin II receptor (AT1 receptor) antagonist, candesartan, (1 mg/kg of body weight per day SC for 2 days) markedly decreased the abundance of the alpha subunit of the epithelial sodium channel (ENaC). This subunit has been shown to be rate-limiting for assembly of mature ENaC complexes. In addition, systemic infusion of angiotensin II increased alphaENaC protein abundance in rat kidney cortex. The decrease in alphaENaC protein abundance in response to AT1 receptor blockade was associated with a fall in alphaENaC mRNA abundance (real-time RT-PCR), consistent with transcriptionally mediated regulation. The effect of AT1 receptor blockade on alphaENaC expression was not blocked by spironolactone, suggesting a direct role of the AT1 receptor in regulation of alphaENaC gene expression. Candesartan administration was also found to increase the abundances of the beta and gamma subunits. The increase in beta and gammaENaC protein abundance was not associated with a significant increase in the renal abundances of the corresponding mRNAs, suggesting a posttranscriptional mechanism. Immunocytochemistry confirmed the increase in beta and gammaENaC protein abundance and demonstrated candesartan-induced ENaC internalization in collecting duct cells. The results support the view that the angiotensin II receptor regulates ENaC abundance, consistent with a role for angiotensin II in regulation of collecting duct function.
 ...
PMID:Long-term regulation of ENaC expression in kidney by angiotensin II. 1268 79

Angiotensin II (ANG II) plays an important role in the development of obstructive nephropathy. Here, we examined the effects of the ANG II receptor type 1 (AT1R) blockade using candesartan on long-term renal molecular and functional changes in response to partial unilateral ureteral obstruction (PUUO). Newborn rats were subjected to severe PUUO or sham operation (Sham) within the first 48 h of life. Candesartan was provided in the drinking water (10 mg.kg(-1).day(-1)) from day 21 of life until 10 wk of age. Renal blood flow (RBF) was evaluated by MRI, glomerular filtration rate (GFR) was measured using the renal clearance of (51)Cr-EDTA, and the renal expression of Na-K-ATPase and the collecting duct water channel aquaporin-2 (AQP2) was examined by immunoblotting and immunocytochemistry. At 10 wk of age, PUUO significantly reduced RBF (0.8 +/- 0.1 vs. 1.6 +/- 0.1 ml.min(-1).100 g body wt(-1); P < 0.05) and GFR (37 +/- 16 vs. 448 +/- 111 microl.min(-1).100 g body wt(-1); P < 0.05) compared with Sham. Candesartan prevented the RBF reduction (PUUO+CAN: 1.6 +/- 0.2 vs. PUUO: 0.8 +/- 0.1 ml.min(-1).100 g body wt(-1); P < 0.05) and attenuated the GFR reduction (PUUO+CAN: 265 +/- 68 vs. PUUO: 37 +/- 16 microl.min(-1).100 g body wt(-1); P < 0.05). PUUO was also associated with a significant downregulation in the expression of Na-K-ATPase (75 +/- 12 vs. 100 +/- 5%, P < 0.05) and AQP2 (52 +/- 15 vs. 100 +/- 4%, P < 0.05), which were also prevented by candesartan (Na-K-ATPase: 103 +/- 8 vs. 100 +/- 5% and AQP2: 74 +/- 13 vs. 100 +/- 4%). These findings were confirmed by immunocytochemistry. Consistent with this, candesartan treatment partly prevented the reduction in solute free water reabsorption and attenuated fractional sodium excretion in rats with PUUO. In conclusion, candesartan prevents or attenuates the reduction in RBF, GFR and dysregulation of AQP2 and Na-K-ATPase in response to congenital PUUO in rats, suggesting that AT1R blockade may protect the neonatally obstructed kidney against development of obstructive nephropathy.
 ...
PMID:Candesartan prevents long-term impairment of renal function in response to neonatal partial unilateral ureteral obstruction. 1703 40

Heart failure (HF) was induced by ligation of the left anterior descending artery (LAD). Left ventricular end-diastolic pressure (LVEDP) >25 mmHg (at day 23 after LAD ligation) was the inclusion criterion. The rats were divided into three groups: sham-operated (Sham, n = 23, LVEDP: 5.6 +/- 0.6 mmHg), HF (n = 14, LVEDP: 29.4 +/- 1.4 mmHg), and candesartan (1 mg.kg(-1).day(-1) sc)-treated HF (HF + Can, n = 9, LVEDP: 29.2 +/- 1.2 mmHg). After 7 days (i.e., 29 days after LAD ligation) semiquantitative immunoblotting revealed increased abundance of inner medulla aquaporin-2 (AQP2) and AQP2 phosphorylated at Ser(256) (p-AQP2) in HF. There was also markedly enhanced apical targeting of AQP2 and p-AQP2 in inner medullary collecting duct (IMCD) in HF compared with Sham rats, shown by immunocytochemistry. Candesartan treatment significantly reversed the increases in both AQP2 and p-AQP2 expression and targeting. In contrast, there were only modest changes in other collecting duct segments. Semiquantitative immunoblots revealed increased expression of type 3 Na(+)/H(+) exchanger (NHE3) and Na(+)-K(+)-2Cl(-) cotransporter (NKCC2) in kidneys from HF compared with Sham rats: both effects were reversed or prevented by candesartan treatment. The protein abundance of alpha-epithelial sodium channel (alpha-ENaC) was increased while beta-ENaC and gamma-ENaC expression was decreased in the cortex and outer stripe of the outer medulla in HF compared with Sham rats, which was partially reversed by candesartan treatment. These findings strongly support an important role of angiotensin II in the pathophysiology of renal water and sodium retention associated with HF.
 ...
PMID:Changes of renal AQP2, ENaC, and NHE3 in experimentally induced heart failure: response to angiotensin II AT1 receptor blockade. 1977 75