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 diverse biological actions of endothelins (ET) appear to be mediated by specific cell-surface receptors. Autoradiography and membrane binding studies have shown abundant ET binding sites in the kidney. However, their expression in specific types of renal cells is unclear. We studied the binding of 125I-labelled endothelin-1 in freshly isolated cell suspensions from canine inner medullary collecting duct. Competition binding experiments revealed the presence of specific high-affinity binding sites: unlabelled ET-1 and ET-2 compared with the radioligand with an IC50 of 135 and 83 pM, respectively, while the IC50 of ET-3 and big ET-1 were 2 and 4 orders of magnitude higher, indicating the presence of ETA-type receptor. Angiotensin II, vasopressin, and atrial natriuretic peptide (ANP) did not compete for ET binding even at a concentration of 10(-6) M. Saturation binding experiments showed a single class of binding sites of high density (Bmax = 56.7 +/- 10.3 fmol/10(6) cells) and high affinity (Kd = 69.8 +/- 10 pM). In contrast, ANP receptors in the same cell preparations appeared as two classes of binding sites with widely different affinity and density. The high-affinity ANP site (Kd = 311 +/- 48 pM) was compatible with ANP-B (guanylate cyclase-coupled) receptor. ET-1 did not compete for this receptor. ET-1 (10(-7) M) did not alter ANP-induced cGMP generation in these cells (3.8-fold increase at 10(-7) M ANP), nor basal levels of cGMP.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Specific endothelin binding sites in renal medullary collecting duct cells: lack of interaction with ANP binding and cGMP signalling. 128 83

Endothelin-1 inhibits sodium and water transport systems in the inner medullary collecting duct. Endothelin-1 levels are reduced in the medulla of spontaneously hypertensive rats (SHR), raising the possibility that decreased inner medullary collecting duct production of endothelin-1 could contribute to inappropriate sodium and water retention. In the current study, immunoreactive endothelin-1 was measured in the urine, blood, and eluates from cortex and outer and inner medulla of SHR before (age 3-4 weeks) and after (age 8-9 weeks) the development of hypertension and in age-matched Wistar-Kyoto (WKY) controls. There was no difference in endothelin-1 levels between prehypertensive SHR and WKY rats. In contrast, 8-9-week-old SHR had significantly reduced endothelin-1 in the urine and outer and inner medulla, but not in the cortex or serum compared with those of WKY controls. Furthermore, inner medullary collecting duct cells from 8-9-week-old SHR, either acutely isolated or cultured, released less endothelin-1 than did those from WKY rats. Finally, the level of endothelin-1 messenger RNA was only reduced in the inner medulla and in inner medullary collecting duct cells from 8-9-week-old SHR. In summary, renal medullary, and in particular terminal collecting duct, endothelin-1 production is reduced in SHR only after the development of hypertension. Such decreases in inner medullary collecting duct endothelin-1 production may contribute to the hypertensive state in SHR.
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PMID:Alterations in renal endothelin-1 production in the spontaneously hypertensive rat. 142 17

We investigated the effects of endothelin-1 (ET-1) on Madin-Darby canine kidney (MDCK) cells, a cell line originating from the renal collecting duct. The activity of transepithelial transport was assessed as the rate of dome formation in monolayers grown on solid support. The pH value of the dome fluid (dome pH) was measured by means of pH-selective microelectrodes. Differentiation of monolayer cells was estimated as the peanut-lectin(PNA)-binding capacity of the apical membrane. Confluent monolayers were incubated for 12-72 h in serum-free medium at various concentrations of ET-1. Exposure to 1 nmol/l ET-1 reduced dome formation by a maximum of 41 +/- 8% (n = 4; P less than 0.02) after 24 h. ET-1 (10 nmol/l; 24 h) decreased dome pH from 7.52 +/- 0.02 (n = 53) to 7.36 +/- 0.03 (n = 51; P less than 0.02). Apical application of amiloride (1 mmol/l) reduced dome pH in both ET-1-treated and non-treated domes to essentially the same level, 7.25 +/- 0.03 (n = 19) and 7.23 +/- 0.03 (n = 17) respectively. ET-1 (10 nmol/l; 24 h) reduced PNA-binding capacity by 19 +/- 3% (n = 5; P less than 0.02). Moreover, ET-1 prevented the increase in PNA binding (+ 53 +/- 7%; n = 5) induced by 0.1 mumol/l aldosterone. We conclude that ET-1 inhibits transepithelial transport and PNA binding via inhibition of apical Na+/H+ exchange, thus antagonizing aldosterone action in MDCK cells.
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PMID:Endothelin-1 blunts transepithelial transport and differentiation of Madin-Darby canine kidney cells. 161 24

Mechanisms of prepro-ET-1 mRNA expression and mature endothelin-1 (ET-1) peptide secretion in MDCK cells (dog collecting duct origin) were investigated. MDCK cells constitutively expressed prepro-ET-1 mRNA (approximately 2.3 kb). TGF-beta time-dependently increased prepro-ET-1 mRNA levels between 30 min and 6 h. Induction of the mRNA 6 h following TGF-beta addition was dose-dependent with a half-maximal concentration of 10 pM. The half-life of prepro-ET-1 mRNA was 15 min in controls when the cells were treated with 10 micrograms/ml of actinomycin D, whereas it was extended to 30-45 min by TGF-beta treatment. Prepro-ET-1 mRNA was rapidly (15-30 min) induced by 0.5 microM TPA, one of the phorbol esters, but downregulated below baseline after 1 h. Our data show that MDCK cells constitutively secrete ET-1 and increase its production in response to TGF-beta. An axis of TGF-beta-ET-1-collecting duct may play an important role in regulation of electrolyte transport and cell growth of the renal tubules.
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PMID:Mechanisms of endothelin-1 mRNA and peptides induction by TGF-beta and TPA in MDCK cells. 172 39

Endothelin has been shown to affect a broad range of renal functions, including rat inner medullary collecting duct Na/K ATPase activity, renin release, renal blood flow, and glomerular filtration rate. The source of endothelin in the kidney has been assumed to be endothelial cells. However, the inner medulla contains the highest concentration of immunoreactive endothelin in the kidney. Additionally, MDCK cells, a distal tubule-like cell line, synthesize endothelin. In order to determine if primary renal tubule cells release endothelin, supernatants collected from rat inner medullary collecting duct cells in culture were tested for endothelin-1 detected by specific radioimmunoassay. Inner medullary collecting duct cells produced endothelin-1 in a time-dependent manner, releasing 1,016.7 +/- 60.1 pg of endothelin-1 per mg/cell protein/24 h. Inner medullary collecting duct cells expressed a 2.2-kilobase mRNA on blot hybridization with rat prepro endothelin-1 cDNA. Vasopressin, thrombin, bradykinin, and epinephrine did not affect endothelin-1 release. These data demonstrate endothelin-1 production by inner medullary collecting duct cells and suggest a possible autocrine role for the peptide.
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PMID:Endothelin synthesis by rat inner medullary collecting duct cells. 195 27

Exogenous endothelin-1 (ET-1) inhibits arginine vasopressin (AVP)-induced cAMP accumulation in the inner medullary collecting duct (IMCD). Because ET-1 is produced by and binds to specific receptors on the IMCD, the possibility exists that ET-1 is an autocrine regulator of AVP action in this nephron segment. To test this hypothesis, rat IMCD cells were grown on semipermeable membranes in the presence of rabbit anti-ET-1 antiserum or nonimmune rabbit serum (NRS). AVP (10(-9) M) caused a 2.5-fold greater accumulation of cAMP in confluent IMCD monolayers preincubated in ET-1 antiserum in comparison with NRS. ET-1 (10(-8) M) inhibited the AVP-induced rise in cAMP by 65% in cells preincubated in ET-1 antiserum but had no effect in NRS-treated cells. Finally, [125I]-ET-1 (30 pM) binding was increased sixfold in IMCD preincubated in anti-ET-1 antiserum. These data indicate that ET-1 causes tonic autocrine inhibition of AVP responsiveness in the IMCD.
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PMID:Autocrine role of endothelin in rat inner medullary collecting duct: inhibition of AVP-induced cAMP accumulation. 750 36

Alterations in the renal metabolism and/or actions of endothelin-1 (ET-1) may be involved in the pathogenesis and maintenance of essential and renal parenchymal hypertension. ET-1 has the potential to modify a broad range of renal functions involved in controlling systemic blood pressure. First, the kidney clears a large percentage of ET-1 from the blood; decreased renal ET-1 clearance may contribute to hypertension occurring in the setting of chronic renal failure. Second, ET-1 potently constricts the renal vasculature resulting in increased fluid retention and possibly contributing to glomerular sclerosis; enhanced renal vascular and glomerular ET-1 production and target cell actions may play a role in essential hypertension or hypertension accompanying chronic renal failure, cyclosporine administration, or erythropoietin therapy. Lastly, ET-1 is also an autocrine inhibitor of collecting duct sodium and water reabsorption; reduced nephron ET-1 production may result in fluid retention in essential hypertension. Determination of the true role that ET-1 plays in the pathogenesis of the varied forms of hypertension awaits the development of safe, potent, and specific endothelin antagonists.
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PMID:Role of intrarenal endothelin in the generation and maintenance of hypertension. 756 83

By using a radioimmunoassay specific for endothelin-1 (ET-1), we measured urinary excretion of ET-1-like immunoreactivity in 63 spot urine samples of 48 patients with primary vesicoureteral reflux (VUR). Urinary excretion of N-acetyl-beta-D-glucosaminidase (NAG), beta 2-microglobulin (beta 2-MG), microalbumin (Alb), and creatinine (Cr) were also measured. There was no significant correlation in any pairs of ET-1 and NAG, ET-1 and beta 2-MG or ET-1 and Alb. In patients with grade 2, grade 3, and grade 4 VUR, urinary ET-1/Cr was significantly higher than normal (p < 0.05). Comparing the grade of reflux according to the International Classification with urinary ET-1/Cr, the ratio of more than normal urinary ET-1/Cr increased in proportion to the grade of reflux, but it conversely decreased in grade 5. In conclusion, urinary ET-1 may be an indicator of distal renal tubular or collecting duct injury in patients with primary VUR.
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PMID:Measurement of urinary endothelin-1-like immunoreactivity and comparison with other urinary parameters in patients with primary vesicoureteral reflux. A preliminary report. 805 26

Nitric oxide (NO), guanosine 3',5'-cyclic monophosphate (cGMP), and endothelin-1 (ET-1) inhibit collecting duct sodium reabsorption. Because the inner medullary collecting duct (IMCD) synthesizes NO and ET-1, we examined NO and cGMP regulation of IMCD ET-1 production. S-nitroso-N-acetylpenicillamine (SNAP, 6 h) increased NO and cGMP and modestly reduced ET-1 release in cultured rat IMCD. Atrial natriuretic peptide or dibutyryl cGMP (6 h exposure to each) also mildly decreased IMCD ET-1 release. In long-term exposure studies, IMCD cells were incubated with tumor necrosis factor (TNF) and interferon-gamma (IFN) up to 72 h. IFN/TNF increased NO and cGMP production while reducing ET-1 release by 84%; N-monomethyl-L-arginine inhibited this effect only marginally, suggesting NO was not primarily involved. IFN alone greatly reduced IMCD ET-1 release and ET-1 mRNA levels. These data indicate that short- and long-term increases in NO and cGMP modestly reduce IMCD ET-1 production. Additionally, IFN potently inhibits IMCD ET-1 release by an undetermined mechanism.
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PMID:Endothelin-1 production by rat inner medullary collecting duct: effect of nitric oxide, cGMP, and immune cytokines. 814 30

We tested the effects of endothelin-1 (ET-1) on intracellular calcium concentration ([Ca2+]i) of cultured M-1 mouse cortical collecting duct cells. [Ca2+]i was measured using fura 2 and a fluorescent imaging system. At a concentration of extracellular calcium ([Ca2+]o) of 1 mM, ET-1 (10(-12) to 10(-7) M) increased [Ca2+]i. A second application of ET-1 had no effect on Ca2+. In contrast, application of arginine vasopressin after an initial exposure to ET-1 induced a second Ca2+ response. In the absence of extracellular Ca2+ (1 mM EGTA) ET-1 also elicited a Ca2+ peak, indicating participation of Ca2+ release from intracellular stores in the initial Ca2+ peak. At [Ca2+]o of 10 mM, ET-1 also induced an intracellular Ca2+ peak but [Ca2+]i remained significantly elevated. The Ca2+ plateau phase was abolished by nickel (10 or 100 microM) and nifedipine (0.1 or 1 microM). We conclude that ET-1 mediates an increase in [Ca2+]i by Ca2+ release from intracellular stores and activation of a nickel- and nifedipine-sensitive Ca2+ entry mechanism.
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PMID:Endothelin increases [Ca2+]i in M-1 mouse cortical collecting duct cells by a dual mechanism. 836 64


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