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

Angiotensin II (ANG II) plays an important role in the regulation of solute transport in the kidney, and its effect on proximal tubule sodium and fluid transport has been studied extensively. Although there is evidence that ANG II receptors are present also in the distal nephron and collecting duct, little is known about the physiological role of ANG II in these segments of the renal tubule. Preliminary studies in our laboratory suggest that ANG II may have both structural and functional effects on intercalated cells in the cortical collecting duct (CCD). Therefore, the present study examines the effect of ANG II on H(+)-adenosinetriphosphatase (H(+)-ATPase) and H(+)-K(+)-ATPase activity in individual CCD segments microdissected from collagenase-treated rat kidneys. The H(+)-ATPase was measured as bafilomycin-sensitive ATPase activity, and H(+)-K(+)-ATPase was measured as Sch-28080-sensitive ATPase activity, by a fluorometric microassay. Preincubation of CCD segments with ANG II, 10(-10)-10(-5) M, caused a dose-dependent decrease in H(+)-ATPase activity with maximum inhibition at 10(-8) M of ANG II. The inhibitory effect of ANG II was abolished when tubules were incubated with ANG II in the presence of 10(-6) M losartan, indicating that the inhibition was mediated via specific AT1 receptors. The AT2-receptor antagonist, PD-123319, had no effect on the ANG II-mediated inhibition of H(+)-ATPase activity. Preincubation of CCD segments with 10(-10) or 10(-7) M ANG II had no effect on H(+)-K(+)-ATPase activity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Angiotensin II regulates H(+)-ATPase activity in rat cortical collecting duct. 781 Jun 90

Because angiotensin II (Ang II) has been found at high concentrations in the proximal tubule fluid and because tubular brush border membranes exhibit a marked capacity for degrading Ang II, we thought it of interest to examine the binding sites for Ang II (3-8) (referred to as Ang IV), a metabolite of Ang II, downstream in the nephron. We studied the binding of [125I]-Ang IV and also of [125I]-Sar1, Ala8, Ang II to SV-40 transformed human collecting duct cell (HCD) membranes. No specific binding site for [125I]-Sar1, Ala8, Ang II and no Ang II-dependent cytosolic calcium response could be observed. Moreover, no signal for the human type I Ang II receptor (hAT1) mRNA was present in HCD cells. In contrast, [125I]-Ang IV bound specifically to HCD cell membranes. Mean Kd and Bmax values derived from saturation binding studies were 5.6 +/- 2.0 nM and 1007.6 +/- 140.2 fmol/mg protein, respectively. The rank order of affinity for competitive Ang II-related peptides was: Ang IV > Ang III > Ang II > Ang II (4-8) > Ang II (1-7). [125I]-Ang IV binding was not modified by nonpeptide AT1 (losartan) or AT2 (PD123177) antagonists. GTP gamma S and dithiotreitol did not affect [125I]-Ang IV binding. Ang IV stimulated cAMP production by intact HCD cells in the presence of forskolin but did not modify cGMP production or cytosolic calcium concentration. Taken together, these results indicate that HCD cells represent a target site for Ang IV but do not possess Ang II receptors.
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PMID:Evidence for angiotensin IV receptors in human collecting duct cells. 888 69

The localization of two type 1 angiotensin II receptor subtype mRNA, AT1A and AT1B, was determined by reverse transcription-PCR on microdissected glomeruli and nephron segments. The coupling sensitivity of these two receptor subtypes was evaluated by measuring variations in intracellular calcium ([Ca2+]i) elicited by angiotensin II (Ang II) in structures expressing either AT1A or AT1B mRNA, using Fura-2 fluorescence. The highest expression of AT1 mRNA was found in glomerulus, proximal tubule, and thick ascending limb. In glomerulus, AT1A and AT1B mRNA were similarly expressed, whereas in all nephron segments AT1A mRNA expression was dominant (approximately 84%). The increase in [Ca2+]i elicited by 10(-7) mol/L Ang II was highest in proximal segments (delta [Ca2+]i is approximately equivalent to 300 to 400 nmol/L) and thick ascending limb (delta [Ca2+]i is approximately equivalent to 200 nmol/L). In glomerulus and collecting duct, the response was lower (delta < 100 nmol/L). The median effective concentrations for Ang II were of the same order of magnitude in glomerulus (12.2 nmol/L), in which both AT1A and AT1B are expressed, and in cortical thick ascending limb (10.3 nmol/ L), in which AT1A is almost exclusively expressed. The Ang II-induced calcium responses were totally abolished by the AT1 receptor antagonist losartan (1 mumol/L) but not by the AT2 antagonist PD 123319 (1 mumol/L). In the absence of external Ca2+, the peak phase of the response induced by 10(-7) mol/L Ang II was reduced and shortened, suggesting that a part of the [Ca2+]i increase originated from the mobilization of the intracellular Ca2+ pool. In conclusion, these results demonstrate that in the rat kidney: (1) AT1A is the predominant AT1 receptor subtype expressed in the nephron segments, (2) glomerulus is the only structure with a relatively high AT1B mRNA content, and (3) AT1A and AT1B receptor subtypes do not differ in their efficiency for the activation of calcium second-messenger system.
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PMID:Expression of type 1 angiotensin II receptor subtypes and angiotensin II-induced calcium mobilization along the rat nephron. 935 68

The interaction of ANG II with intrarenal AT1 receptors has been implicated in the progression of diabetic nephropathy, but the role of intrarenal AT2 receptors is unknown. The present studies determined the effect of early diabetes on components of the glomerular renin-angiotensin system and on expression of kidney AT2 receptors. Three groups of rats were studied after 2 wk: 1) control (C), 2) streptozotocin (STZ)-induced diabetic (D), and 3) STZ-induced diabetic with insulin implant (D+I), to maintain normoglycemia. By competitive RT-PCR, early diabetes had no significant effect on glomerular mRNA expression for renin, angiotensinogen, or angiotensin-converting enzyme (ACE). In isolated glomeruli, nonglycosylated (41-kDa) AT1 receptor protein expression (AT1A and AT1B) was increased in D rats, with no change in glycosylated (53-kDa) AT1 receptor protein or in AT1 receptor mRNA. By contrast, STZ diabetes caused a significant decrease in glomerular AT2 receptor protein expression (47.0 +/- 6.5% of C; P < 0.001; n = 6), with partial reversal in D+I rats. In normal rat kidney, AT2 receptor immunostaining was localized to glomerular endothelial cells and tubular epithelial cells in the cortex, interstitial, and tubular cells in the outer medulla, and inner medullary collecting duct cells. STZ diabetes caused a significant decrease in AT2 receptor immunostaining in all kidney regions, an effect partially reversed in D+I rats. In summary, early diabetes has no effect on glomerular mRNA expression for renin, angiotensinogen, or ACE. AT2 receptors are present in glomeruli and are downregulated in early diabetes, as are all kidney AT2 receptors. Our data suggest that alterations in the balance of kidney AT1 and AT2 receptor expression may contribute to ANG II-mediated glomerular injury in progressive diabetic nephropathy.
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PMID:Early streptozotocin-diabetes mellitus downregulates rat kidney AT2 receptors. 1120 1

Angiotensin-(1-7) (Ang-[1-7]) is a heptapeptide member of the renin-angiotensin system (RAS), and acts as a vasodilator and antagonist of angiotensin II (Ang II) in the vasculature. The role of Ang-(1-7) in regulating kidney function is not well understood. Within the kidneys, Ang-(1-7) is generated by angiotensin-converting enzyme 2 (ACE2)-mediated degradation of Ang II, sequential cleavage of the precursor angiotensin I (Ang I) by ACE2 and ACE, or the actions of brush-border membrane peptidases on Ang I. Ang-(1-7) mediates its effects via binding to kidney Mas receptors, although some actions may occur via Ang II AT1 or AT2 receptors. In vitro studies suggest that Ang-(1-7) is an intrarenal vasodilator. Ang-(1-7) has been reported to induce either natriuresis/diuresis or sodium and water retention, via modulation of sodium transporters in the proximal tubule and loop of Henle, and collecting duct water transport. In the proximal tubule, Ang-(1-7) antagonizes growth-promoting signaling pathways via activation of a protein tyrosine phosphatase, whereas in mesangial cells, Ang-(1-7) stimulates cell growth via activation of mitogen-activated protein kinases. The phenotype of the Mas gene knockout mouse suggests that Ang-(1-7)-signaling events exert cardiovascular protection by regulating blood pressure, and by limiting production of reactive oxygen species and extracellular matrix proteins. Ang-(1-7) also protects against renal injury in the renal wrap hypertension model, independent of effects on blood pressure. In diabetic nephropathy, however, the role of Ang-(1-7) on disease progression remains unclear. In summary, Ang-(1-7) and its receptor Mas have emerged as important components of the intrarenal RAS. The signaling and downstream effects of Ang-(1-7) in the kidney are complex and appear to be cell specific. The body of evidence suggests that Ang-(1-7) is protective against endothelial dysfunction or Ang II-stimulated proximal tubular injury, although the overall effects on glomerular function require further study.
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PMID:Angiotensin-(1-7) and its effects in the kidney. 1957 9