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)

Endothelium-derived relaxing factor (EDRF) has profound effects on the renal vasculature, the glomerular mesangium, and also affects renal salt excretion. EDRF stimulates guanylyl cyclases, which are thought to be heterodimers comprised of alpha and beta subunits. Two alpha and two beta isoforms have been identified thus far. However, the molecular composition of in vivo guanylyl cyclase-linked EDRF receptors is unknown. We used polymerase chain reaction to clone a portion of the rat alpha 2 subunit. Guanylyl cyclase-linked EDRF receptor mRNA was detected in microdissected renal structures using a reverse transcription/polymerase chain reaction assay. The interlobular artery/afferent arteriole contained mRNA for the alpha 1, alpha 2, and beta 1 subunits; a faint beta 2 band was found in 29% of experiments. In contrast, the cortical collecting duct contained mRNA only for alpha 1 and beta 2 subunits. We conclude that guanylyl cyclase-linked EDRF receptor subunit isoforms are independently and heterogeneously expressed in the renal vasculature and cortical collecting duct, suggesting that several different EDRF receptors exist in vivo. These data suggest that the tubule receptor is composed of alpha 1/beta 2. The vasculature may contain at least two different EDRF receptors (alpha 1/beta 1 and alpha 2/beta 1). Some beta 2 may also be expressed, allowing for even greater heterogeneity.
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PMID:Differential expression of mRNA for guanylyl cyclase-linked endothelium-derived relaxing factor receptor subunits in rat kidney. 809

A selective antagonist for the cGMP-linked ANF receptor was used to assess inhibition of cardiovascular and renal actions of atrial natriuretic factor (ANF). Two groups of anesthetized rats were injected with antagonist or vehicle, respectively, prior to an infusion of ANF. A third group received neither antagonist injection nor ANF infusion and served as a time control. Compared to ANF infusion alone, prior antagonist administration was associated with significant reduction of both the hypotension and hemoconcentration following peptide infusion, although significant residual effects were still present. Glomerular filtration rates during ANF infusion were significantly lower in the antagonist group. The increases in urinary salt and water excretion were also partially blocked by the antagonist. Microcatheterization studies showed significant partial reversal of ANF-induced inhibition of sodium chloride and water reabsorption in the medullary collecting duct. We conclude that the antagonist is an effective specific blocker of the cardiovascular, renal hemodynamic, and tubular effects of ANF, providing a useful new tool to elucidate the regulatory roles of this peptide hormone system.
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PMID:Cardiovascular and renal functional effects of an antagonist of the guanylyl cyclase-linked ANF receptor. 814 Feb 74

We examined the actions of potentially natriuretic autacoids in the isolated perfused cortical collecting duct (CCD) dissected from inbred Dahl (Rapp strain) salt-sensitive rats (SS). Atrial natriuretic peptide (ANP, 10 nM), bradykinin (BK, 10 nM), and clonidine (1 microM) were studied to determine their effects on the lumen-to-bath flux of 22Na+ (J1-->b, pmol min-1 mm-1), hydraulic conductivity (Pf, micron/s), and transepithelial voltage (VT, mV). ANP and BK have been shown by others to significantly reduce net Na+ reabsorption and hydraulic conductivity in the Sprague-Dawley (SD) rat CCD, but previous results from our laboratory showed no ANP or BK effect in the SD CCD. In the present study, we were also unable to observe any effect of either ANP or BK in the SS rat CCD. However, in the presence of AVP, clonidine (a partial alpha 2-adrenergic receptor agonist) significantly reduced J1-->b and Pf from 139 +/- 6 (SEM) to 88 +/- 7 and from 959 +/- 176 to 490 +/- 73, respectively. In addition, clonidine significantly depolarized VT from -14.5 +/- 2.8 to -11.2 +/- 1.8. However, unlike its effects in the SD rat CCD, yohimbine (300 nM, an alpha 2-adrenergic receptor antagonist) did not significantly reverse the effects of clonidine on J1-->b, Pf or VT in the SS rat CCD.
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PMID:Clonidine, but not bradykinin or ANP, inhibits Na+ and water transport in Dahl SS rat CCD. 835 63

By using an in vitro microperfusion technique, we examined whether a novel loop diuretic, 7-Chloro-2,3-dihydro-1-(2-methylbenzoyl)-4(IH)-quinolinone-4-oxime-o-sul fonic acid, potassium salt (M17055), a derivative of quinolinone oxime sulfonic acids, affects Na+ and K+ transport in the distal nephron segments, including the cortical collecting duct and connecting tubule (CNT) isolated from rabbit kidneys. M17055 added to the lumen at 1 mM caused a positive deflection of transepithelial voltage (VT) by 2.2 +/- 0.4 mV. The response was less than that evoked by 10 microM amiloride (8.9 +/- 0.1 mV). In the collecting duct cell of the cortical collecting duct from normal rabbits, M17055 depolarized the basolateral membrane by 9.2 +/- 1.3 mV, whereas amiloride hyperpolarized it by 7.6 +/- 2.4 mV. In the cortical collecting duct from deoxycorticosterone acetate-treated rabbits, despite the fact that both agents depolarized the basolateral membrane of the collecting duct cell, amiloride consistently hyperpolarized the apical membrane, whereas M17055 did not cause any significant changes in apical membrane voltage. In the presence of 2mM Ba++ in the lumen, the apical membrane voltage deflection by M17055 was abolished. In addition, the magnitude of the apical membrane voltage deflection caused by an abrupt increase in luminal K+ concentration from 5 to 50 mM was significantly reduced. In the CNT, both amiloride and M17055 caused a positive deflection of VT. However, M17055 depolarized the basolateral membrane by 6.6 +/- 1.6 mV, whereas amiloride hyperpolarized it by 4.4 +/- 1.1 mV.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of a novel diuretic, 7-chloro-2,3-dihydro-1-(2-methylbenzoyl)-4(IH)-quinolinone-4-oxime-o- sulfonic acid, potassium salt (M17055) on Na+ and K+ transport in the distal nephron segments. 839 38

We studied the natriuretic effects of a combined mannitol and atrial natriuretic peptide (ANP) infusion in chronic caval dogs (TIVC) either responsive or unresponsive to an initial ANP infusion (75 ng.kg-1.min-1). The increment in urinary Na+ excretion (delta UNaV) to the initial ANP infusion in 11 TIVC responders was 127 and 1 mu eq/min in 7 nonresponders. A modest mannitol dose was then infused so as to augment distal Na+ delivery to the distal nephron but not flood the terminal inner medullary collecting duct (IMCD) with enormous quantities of salt and water. After mannitol, UNaV was 26 +/- 8 mu eq/min in TIVC responders and 24 +/- 4 mu eq/min in nonresponders. In these two groups of dogs, delta UNaV after manitol was 13 and 10 mu eq/min, respectively, from the previous experimental phase. During this stable mannitol-induced modest natriuresis, ANP was reinfused at initial dose levels. In TIVC responders, delta UNaV was 186 mu eq/min, a value greater than that obtained initially (P < 0.05), and delta UNaV in nonresponders was now 52 mu eq/min (P < 0.05). Because control and postmanitol UNaV was equivalent for each group, in the face of similar levels of glomerular filtration rate, blood pressure, and renal perfusion, it is difficult to conclude that only augmented delivery of Na+ to the IMCD converted TIVC nonresponders into responding dogs after mannitol and ANP. Other modulating factors may be involved.
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PMID:Urinary sodium excretion in chronic caval dogs after combined infusions of mannitol and ANP. 844 33

This study tested the hypothesis that intrarenal kinins play a regulatory role in electrolyte excretion by altering Cl- absorption in the collecting duct. We measured Cl- and insulin concentrations in tubular fluid samples obtained from medullary collecting ducts (MCD) of Dahl/Rapp salt-resistant (SR/ Jr) rats by microcatheterization of ducts of Bellini before and after treatment with the bradykinin receptor antagonist HOE-140. Tubular fluid was obtained from paired terminal inner medullary (t-IMCD) and outer medullary (OMCD) collecting duct sites of the left kidney. HOE-140 (n = 7) or vehicle (n = 5) was infused intravenously, and the collections were repeated. HOE-140 did not alter glomerular filtration rate but decreased urine flow rate (P < 0.05) and absolute and fractional Cl- excretion (P < 0.01). HOE-140 did not alter the fraction of filtered Cl- delivered (FDCl) to the OMCD but decreased FDCl to the t-IMCD from 2.3 +/- 0.3 to 1.3 +/- 0.3% (P < 0.05). The fraction of filtered Cl- absorbed per millimeter between the collection sites was increased from 0.2 +/- 0.1 to 0.6 +/- 0.1% (P < 0.05). Fractional absorption of water along the MCD was also increased (P < 0.05). No changes in excretory function or tubular Cl- or water absorption were observed in vehicle-treated rats. These studies show that kinin B2 receptor blockade enhances Cl- and water absorption in the MCD, a finding that supports a role of renal kinins in the regulation of NaCl and water excretion.
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PMID:Bradykinin B2 receptor antagonist increases chloride and water absorption in rat medullary collecting duct. 877 Jan 34

The present study was undertaken to investigate the mRNA localization of the two major kidney-specific Na-K-Cl transport proteins, the bumetanide-sensitive cotransporter (NKCC2 in rabbit and BSC1 in rat) and the thiazide-sensitive cotransporter (TSC). NKCC2 from rabbit and mouse has been shown to exist in three isoforms (designated A, B, and F) that differ only in a 96-bp region. The divergent region of each of the three NKCC2 isoforms was cloned from rat kidney by a polymerase chain reaction (PCR)-based strategy, and isoform-specific primers were chosen. RNA and cDNA were prepared from renal cortex and medulla and from microdissected nephron segments. Using reverse transcription (RT)-PCR, the B isoform was detected only in cortex and the F isoform only in medulla, whereas the A from was found in both. In dissected nephron segments, the B form was found exclusively in cortical thick ascending limb (CTAL) and macula densa-containing segment (MDCS), the F form only in medullary thick ascending limb (MTAL) and outer medullary collecting duct, and the A form in CTAL, MDCS, and MTAL. An additional isoform including both A and F exons was identified by direct sequencing of a 592-bp product from medulla. The AF product was found only in the medulla and was localized exclusively in MTAL. TSC mRNA was detected exclusively in the distal convoluted tubule. Differential nephron localization of NKCC2 isoforms suggests that Na-K-Cl cotransporters may differ in their transport characteristics to explain regulation of salt transport along the nephron.
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PMID:Localization of bumetanide- and thiazide-sensitive Na-K-Cl cotransporters along the rat nephron. 889 25

Using a strategy based on homology to the bovine parathyroid Ca(2+)-sensing receptor previously identified by us (5), we have recently isolated an extracellular, G protein-coupled Ca2+/ polyvalent cation-sensing receptor, RaKCaR (22), from rat kidney. The localization and physiological role(s) of this receptor in the kidney are not well understood. In the present study, we assessed the distribution of mRNAs for RaKCaR and the parathyroid hormone/parathyroid hormone-related protein (PTH/PTHrP) receptor along the rat nephron by in situ hybridization and reverse transcriptase-polymerase chain reaction of microdissected nephron segments. Our results show that transcripts for both receptors coexpress at glomeruli, proximal convoluted tubule, proximal straight tubule, cortical thick ascending limb, distal convoluted tubule, and cortical collecting duct. In addition, RaKCaR (but not PTH/PTHrP receptor) transcripts were found in the medullary thick ascending limb and outer medullary and inner medullary collecting ducts. These findings raise the possibility of roles for RaKCaR not only in the regulation of divalent mineral reabsorption but also in water reabsorption and urinary concentration. Taken together, our results provide new insights in understanding the effects of hypercalcemia on hormone-stimulated salt and water transport.
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PMID:Localization of the extracellular Ca(2+)-sensing receptor and PTH/PTHrP receptor in rat kidney. 889 27

Dahl salt-sensitive (S) rats develop hypertension in response to a high-salt diet, whereas Dahl salt-resistant (R) rats do not. There is good evidence that the Dahl S kidneys have diminished natriuretic capacity. We studied the rate of Na+ transport by primary cultures of the inner medullary collecting duct from these two strains to determine whether there were intrinsic differences. Monolayers obtained from prehypertensive S rats transported Na+ at twice the rate as monolayers from age-matched R rats. Mineralocorticoid and glucocorticoid hormones increased Na+ transport from both strains; the S rat monolayers always displayed higher transport rates than R rat monolayers with the same treatment. The Na+ entry pathway in both S and R rat monolayers was via an Na+ channel. The difference in Na+ transport was not explained by a difference in the metabolism of corticosterone, ATP content, citrate synthase activity, ultrastructural appearance, or rate of maturation. Monolayers from S rats tended to have higher protein and DNA content, but these differences could not account for the difference in Na+ transport. Anion secretion in response to adenosine 3',5'-cyclic monophosphate agonists was similar. These results demonstrate intrinsic differences in renal tubular cells that may play an important role in the pathogenesis of salt-sensitive hypertension.
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PMID:IMCD cells cultured from Dahl S rats absorb more Na+ than Dahl R rats. 894 97

Cardiodilatin/atrial natriuretic peptide (CDD/ ANP) is a hormone system of great clinical importance. The prohormone CDD/ANP-1-126 is a peptide synthesized in the heart and cleaved during exocytosis into the circulating form CDD/ANP-99-126. Urodilatin (CDD/ ANP-95-126) is a homologue natriuretic peptide that differs from CDD/ANP-99-126 by four amino acids. Whereas CDD/ANP-99-126 circulates in blood plasma and is not excreted into the urine, urodilatin is detected only in urine. Urodilatin exerts its renal effects in a paracrine fashion. After its secretion from cells in the distal tubule, it interacts with luminally located receptors in the collecting duct, resulting in increased diuresis and natriuresis. Results suggest that urodilatin plays an important role in the physiologic regulation of fluid-balance and sodium homeostasis. Pharmacology studies reveal significant differences when urodilatin and CDD/ANP-99-126 are given intravenously, showing that stronger diuresis and natriuresis are induced by urodilatin as compared with those induced by CDD/ANP-99-126. Clinical studies indicate the prophylactic and therapeutic effect of urodilatin in patients suffering from acute renal failure following heart and liver transplantation. A significant reduction in requirements for hemodialysis/hemofiltration can be achieved using urodilatin. Postobstructive diuresis and natriuresis is probably due to a defective urinary concentrating mechanism and is usually resistant to treatment with antidiuretic hormone. The distal tubule and collecting duct have often been considered to be the site of altered sodium and water excretion following relief of obstruction. Since circulating CDD/ANP-99-126 levels are markedly elevated during obstruction and decrease upon relief of the obstruction, natriuretic peptides may play an important role in this clinical feature. On the basis of recent findings attributing an important role in sodium homeostasis to urodilatin in contrast to CDD/ANP-99-126, future studies have to clarify whether urodilatin, not CDD/ANP-99-126, might be responsible for the altered renal sodium excretion observed in postobstructive diuresis. In the past decade a considerable amount of research has led to the identification and characterization of hormones of the natriuretic peptide family [13]. These peptides are involved in the regulation of salt and water homeostasis. The prototype of the natriuretic hormones is cardiodilatin/atrial natriuretic peptide (CDD/ANP), or A-type natriuretic peptide. CDD/ANP is primarily produced in the heart [6]. It is synthesized as a precursor molecule, CDD/ ANP-1-126, in specific granules in atrial myoendocrine cells [15]. The prohormone, upon appropriate stimuli for release, is cleaved into the C-terminus CDD/ANP-99-126 and excreted into the circulation via exocytosis [16]. Further members of the natriuretic peptide family are brain natriuretic peptide (BNP, or B-type natriuretic peptide) [45] and C-type natriuretic peptide (CNP) [46]. All the members of this family share many common features, including tissue distribution of gene expression, biosynthetic pathways, and pharmacologic effects in target organs [13,26]. The main biologic effects of these hormones are natriuresis, diuresis, and vasodilation [5, 6, 14, 22], but these vary among the individual peptides. Natriuretic effects such as increased glomerular filtration, inhibition of aldosterone production, and secretion result from direct inhibition of sodium absorption in the collecting duct. Urodilatin (INN: Ularitide) is a member of the natriuretic peptide family, discovered in 1988 by Schulz-Knappe et al. [43]. This hormone is presumably synthesized in the kidney and exerts potential paracrine renal effects [17]. Results of clinical phase I-II trials suggest a potent therapeutic effect of urodilatin in the treatment of acute renal failure in patients following organ transplantation [4, 27, 33].
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PMID:The renal paracrine peptide system--possible urologic implications of urodilatin. 898 39


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