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)

The (pro)renin receptor ([P]RR) is a transmembrane protein that binds both renin and prorenin with high affinity, increasing the catalytic cleavage of angiotensinogen and signaling intracellularly through mitogen-activated protein kinase activation. Although initially reported as having no homology with any known membrane protein, other studies have suggested that the (P)RR is an accessory protein, named ATP6ap2, that associates with the vacuolar H(+)-ATPase, a key mediator of final urinary acidification. Using in situ hybridization, immunohistochemistry, and electron microscopy, together with serial sections stained with nephron segment-specific markers, we found that (P)RR mRNA and protein were predominantly expressed in collecting ducts and in the distal nephron. Within collecting ducts, the (P)RR was most abundant in microvilli at the apical surface of A-type intercalated cells. Dual-staining immunofluorescence demonstrated colocalization of the (P)RR with the B1/2 subunit of the vacuolar H(+)-ATPase, the ion exchanger that secretes H(+) ions into the urinary space and that associates with an accessory subunit homologous to the (P)RR. In collecting duct/distal tubule lineage Madin-Darby canine kidney cells, extracellular signal-regulated kinase 1/2 phosphorylation, induced by either renin or prorenin, was attenuated by the selective vacuolar H(+)-ATPase inhibitor bafilomycin. The predominant expression of the (P)RR at the apex of acid-secreting cells in the collecting duct, along with its colocalization and homology with an accessory protein of the vacuolar H(+)-ATPase, suggests that the (P)RR may function primarily in distal nephron H(+) transport, recently noted to be, at least in part, an angiotensin II-dependent phenomenon.
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PMID:The (Pro)renin receptor: site-specific and functional linkage to the vacuolar H+-ATPase in the kidney. 1954 73

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

[Arg(8)]-vasopressin (AVP) has several functions via its three distinct receptors, V1a, V1b, and V2. The V1a vasopressin receptor (V1aR) is expressed in blood vessels and involved in vascular contraction. Recently, we generated V1a receptor-deficient (V1aR(-/-)) mice and found that they were hypotensive. In addition, V1aR(-/-) mice exhibited (1) blunted AVP-induced vasopressor response, (2) impaired arterial baroreceptor reflex, (3) decreased sympathetic nerve activity, and (4) decreased blood volume, all of which could contribute to the observed hypotension. In relation to their decreased blood volume, V1aR(-/-) mice had decreased plasma aldosterone levels, which could result not only from decreased activity of the renin-angiotensin system (RAS), but also from impaired AVP-stimulated aldosterone release in the adrenal glands. V1aR was found to specifically co-express at the macula densa cells with cyclooxygenase (COX)-2 and with neuronal nitric oxide synthase, which produces potent stimulators of renin, PGE(2), and NO. The expression levels of renin, COX-2, and nNOS were significantly decreased in V1aR(-/-) mice, which led to the suppression of RAS activity and consequent decreases in aldosterone and blood volume. Furthermore, V1aR is also expressed in collecting duct cells and involved in regulating water reabsorption by affecting V2/aquaporin 2 function. Thus, AVP regulates blood pressure and volume via V1aR by exerting diverse functions in vivo.
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PMID:Vasopressin regulation of blood pressure and volume: findings from V1a receptor-deficient mice. 1969

E Prostanoid (EP) receptors play an important role in urinary Na(+) excretion. In the kidney, the epithelial sodium channel (ENaC) is the rate-limiting-step for Na(+) reabsorption. We hypothesized that activation of EP1/EP3 regulates the expression of ENaC in the face of renin-angiotensin-aldosterone-system (RAAS) activation. In primary cultures of inner medullary collecting duct (IMCD) cells, sulprostone (EP1>EP3 agonist, 1 microM) and 17 Phenyl trinor (17 Pt, EP1 agonist, 10 microM) prevented the up-regulation of alphaENaC mRNA induced by aldosterone (10 nM). In Sprague-Dawley rats infused with angiotensin II (0.4 microg/kg/min), alphaENaC expression was up-regulated in renal cortex and medulla coincidently with high plasma aldosterone levels. Sulprostone and/or 17 Pt prevented this effect in renal medulla but not in cortex. Immunocytochemistry demonstrated that IMCD cells express EP1. Our results suggest that specific activation of EP1 receptor during RAAS activation antagonizes the action of aldosterone on alphaENaC expression in the renal medulla.
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PMID:E Prostanoid-1 receptor regulates renal medullary alphaENaC in rats infused with angiotensin II. 1973 40

When the succinate receptor (SUCNR1) is activated in the afferent arterioles of the glomerulus it increases renin release and induces hypertension. To study its location in other nephron segments and its role in kidney function, we performed immunohistochemical analysis and found that SUCNR1 is located in the luminal membrane of macula densa cells of the juxtaglomerular apparatus in close proximity to renin-producing granular cells, the cortical thick ascending limb, and cortical and inner medullary collecting duct cells. In order to study its signaling, SUCNR1 was stably expressed in Madin-Darby Canine Kidney (MDCK) cells, where it localized to the apical membrane. Activation of the cells by succinate caused Gq and Gi-mediated intracellular calcium mobilization, transient phosphorylation of extracellular regulated kinase (ERK)1/2 and the release of arachidonic acid along with prostaglandins E2 and I2. Signaling was desensitized without receptor internalization but rapidly resensitized upon succinate removal. Immunohistochemical evidence of phosphorylated ERK1/2 was found in cortical collecting duct cells of wild type but not SUCNR1 knockout streptozotocin-induced diabetic mice, indicating in vivo relevance. Since urinary succinate concentrations in health and disease are in the activation range of the SUCNR1, this receptor can sense succinate in the luminal fluid. Our study suggests that changes in the luminal succinate concentration may regulate several aspects of renal function.
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PMID:Localization of the succinate receptor in the distal nephron and its signaling in polarized MDCK cells. 1977 18

In the setting of primary aldosteronism, elevated aldosterone levels are associated with increased blood pressure. Aldosterone concentrations within the normal range, however, can also alter blood pressure. Furthermore, the aldosterone-to-renin ratio, an indicator of aldosterone excess, is associated with hypertension, even in patients without excessive absolute aldosterone levels. In this Review we assess the data on the role of aldosterone in the development and maintenance of hypertension. We provide an overview of the complex crosstalk between genetic and environmental factors, and about aldosterone-mediated arterial hypertension and target organ damage. The discussion is organized according to major targets of aldosterone action: the collecting duct in the kidney, the vasculature and the central nervous system. The antihypertensive efficacy of mineralocorticoid-receptor blockers, even in patients with aldosterone values in the normal range, supports the evidence that aldosterone plays a part in blood pressure elevation in the absence of primary aldosteronism.
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PMID:Aldosterone and arterial hypertension. 2002 93

Increased extracellular fluid volume (ECF) characterizes compensated cirrhosis. To identify the mechanisms of fluid retention in cirrhosis through clearance methods, 10 control and 10 preascitic rats with CCl(4)-induced cirrhosis were studied following i.v. loading with 1 ml 5% glucose solution. Glomerular filtration rate and renal plasma flow were evaluated through inulin and para-aminohippurate clearances; water and electrolyte handling was assessed measuring urine and plasma osmolarity, electrolyte excretions, and tubular solute-free water reabsorption (TFWR = osmolar clearance minus urinary output); ECF was assessed through hormonal status determination. After water loading, cirrhotic rats had increased ECF (lower plasma renin activity and aldosterone and higher atrial natriuretic peptide levels, all P<0.03), solute-free water retention (increased TFWR and decreased plasma osmolarity, all P<0.05), reduced absolute and fractional sodium excretions (P<0.05). Cirrhotic rats showed sodium retention in the medullary thick ascending limb of Henle's loop (i.e. increased values of TFWR for any given value of osmolar clearance). Trans-tubular potassium gradient in medullary collecting duct was similar in the two groups (P=0.55), ruling out aldosterone-dependent sodium retention and potassium hyper-secretion. In experimental preascitic cirrhosis NaCl retention in the ascending limb of Henle's loop increases medullary interstitial tonicity leading to vasopressin-independent water back-diffusion in thin descending limb of Henle's loop and collecting duct.
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PMID:Solute-free water retention in preascitic cirrhotic rats following intravenous water loading. 2006 4

There are several mysteries about the normal physiology of pregnancy (1). Renal sodium and water reabsorption occurs despite an increase in total blood volume. Moreover, the renin-angiotensin-aldosterone system (RAAS) is also stimulated in normal pregnancy, even though an increase in total blood volume normally suppresses the RAAS and increases sodium excretion in the nonpregnant state. Water retention also occurs and leads to hypoosmolality in normal pregnancy, even though total blood volume is expanded. On rare occasions, an extreme polyuria occurs in pregnancy that is unresponsive to arginine vasopressin (AVP). The receptors whereby AVP and oxytocin stimulate the principal cell of the collecting duct, vascular smooth muscle, glomerular mesangial and endometrial cells are in need of clarification. The present study proposes potential mechanisms relating to systemic arterial vasodilation to explain some of the apparent dilemmas of pregnancy.
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PMID:Dilemmas in human and rat pregnancy: proposed mechanisms relating to arterial vasodilation. 2008 11

(Pro)renin receptor ((P)RR), a specific receptor for renin and prorenin, is a 350 amino-acid protein with a single transmembrane domain and may play important pathophysiological roles in diabetic nephropathy. The aim of the present study is to clarify the expression of (P)RR in the kidney with end-stage renal disease due to diabetic nephropathy. The kidney tissues were obtained at autopsy from patients with and without Type 2 diabetes mellitus (n=5 without diabetes mellitus; and n=8 with diabetes mellitus). Immunocytochemistry showed that (P)RR was mainly expressed in the tubular cells and collecting duct cells of the kidney without diabetic nephropathy. Cells in glomeruli were very weakly and sporadically immunostained for (P)RR. Vascular smooth muscle cells and endothelial cells were very weakly or were not immunostained for (P)RR. Adipocytes in the adipose tissue around the kidney were positively immunostained for (P)RR. Immunostaining pattern of (P)RR in the kidney with diabetic nephropathy was similar to that without diabetic nephropathy. However, most notably, (P)RR immunostaining in the tubular cells and collecting duct cells was clearly and frequently more strongly observed in the kidney with diabetic nephropathy up to the end-stage renal disease. The present study has raised the possibility that (P)RR expressed in the diabetic kidney may play a pathophysiological role in angiotensin I generation and renal fibrosis found in end-stage renal disease.
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PMID:Expression of (pro)renin receptor in human kidneys with end-stage kidney disease due to diabetic nephropathy. 2038 87

Potassium (K+) is a key component of the resting membrane potential of all cells that influences many important biologic events. The clinical importance of K+ is that surpluses or deficits in K+ in the extracellular fluid may predispose the patient to cardiac arrhythmias. The kidneys adjust overall K+ homeostasis by increasing or decreasing the rate of excretion of K+. Urinary excretion of K+ has 2 components: (i) the concentration of K+ in the tubular fluid that depends on the capacity of the cortical collecting duct to secrete K+. The capacity is determined by the lumen-negative transepithelial potential difference generated by the electrogenic reabsorption of Na+. Aldosterone and to a lesser degree HCO3- and Na+ in the tubular fluid are implicated in the generation of the potential difference. This component is evaluated by the transtubular K+ gradient (TTKG). (ii) The volume of fluid delivered to the cortical collecting duct that depends on the osmolar rate of excretion. These 2 components can be calculated if blood osmolality is higher than urine osmolality. Thus, investigating K+ abnormalities is based on the determination of TTKG and osmolar rate of excretion in the cortical collecting duct, on other clinical (extracellular fluid, blood pressure...) and biological data (24-hour K+ excretion, renin, aldosterone...) easily available. First treatment of K+ abnormality is the treatment of its cause. Insulin and glucose supply and dialysis are the best symptomatic treatments of hyperkalaemia.
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PMID:[Potassium physiology, hypokalaemia and hyperkalaemia]. 2039 66


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