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)

A primary culture from rat renal IMCD cells was established to investigate the permeability characteristics of the luminal and contraluminal plasma membranes of the papillary collecting duct in vitro. Freshly isolated IMCD cells were grown on filters in a special "epithelial cell" medium. Confluency was proved with an epithelial volt/ohm meter. After 7 d of culture the transepithelial resistance reached more than 1000 omega x cm2. A polarization of the cells with regard to a basolateral localization of a lactate efflux system, and an L-alanine transport system was achieved. The hypotonicity-activated release systems for the organic osmolytes sorbitol and betaine were also located basolaterally, whereas taurine, glycerophosphorylcholine, and myo-inositol left the cells at both cell poles but with different capacity. Morphological observations revealed also that the monolayer was well differentiated. Thus, a model of a renal collecting duct epithelium was established which can be used to analyze polarized and differentiated transport processes across the epithelial cells and their plasma membranes.
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PMID:Properties of a polarized primary culture from rat renal inner medullary collecting duct (IMCD) cells. 955 40

A novel cDNA encoding a protein kinase (termed PASK) was isolated from rat brain. The PASK catalytic domain was most similar to Ste20-related protein kinases, showing 45.5 and 39.2% amino acid identity with human SOK1 and yeast Sps1, respectively. The amino-terminal noncatalytic domain of 71 amino acids was rich in alanine and proline and contained several proline-alanine repeats. PASK was widely expressed in rat tissues but negligible in liver and skeletal muscle. Immunohistochemical analysis revealed that PASK was localized to a distinct set of cells including neurons, adrenal glomerulosa cells, and transporting epithelia such as epithelial cells of brain choroid plexus, distal tubule and collecting duct of kidney, duct of salivary gland, and parietal cells of stomach. Subcellular fractionation showed that PASK was present in both the cytosol and the Triton X-100-insoluble cytoskeletal fraction in brain.
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PMID:Molecular cloning and characterization of a novel Ste20-related protein kinase enriched in neurons and transporting epithelia. 967 32

Nephrogenic diabetes insipidus (NDI) is associated with germline mutations in two genes: vasopressin receptor type 2 (V2(R)) in X-linked NDI, and the water channel aquaporin-2, in autosomal-recessive disease. Genetic heterogeneity is further emphasized by reports of phenotypically abnormal individuals with normal structural genes. We analyzed both genes in five Brazilian families and the aquaporin-2 gene in two Swedish families with clinical and laboratory diagnosis of NDI, by a combination of denaturing gradient gel electrophoresis (DGGE) and direct DNA sequencing. A novel polymorphism in the aquaporin-2 gene (S167S), but no disease-associated mutations in any tested individual from all seven families, was detected. In two Brazilian families, frameshift mutations were detected in the V2(R) gene: one leading to a premature stop after codon 36 and the other to a longer peptide (462 aa instead of the 373 aa wild-type protein). In two other Brazilian families, probable disease-associated missense mutations were detected: an alanine to proline at codon 163 (A163P) and an asparagine to aspartic acid at codon 85 (D85N). In one Brazilian family, both genes were structurally normal and the aquaporin-2 gene was also normal in the two Swedish kindreds. This report further extends the mutational spectrum of NDI and suggests that there are other mutational or epigenetic events inactivating the two known genes or even novel genes that underlie NDI.
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PMID:Molecular analyses of the vasopressin type 2 receptor and aquaporin-2 genes in Brazilian kindreds with nephrogenic diabetes insipidus. 1047 31

Vasopressin V(2) receptors at high-density and V(1B) receptors are candidates for the V(2)-like receptor, which evokes an increase in [Ca(2+)](i) when stimulated by the vasopressin V(2) receptor agonist 1-desamino-8-D-arginine vasopressin (dDAVP) in kidney inner medullary collecting duct. We compared the pharmacological characteristics of vasopressin V(2) and V(1B) receptors in Chinese hamster ovary (CHO) cells to those of vasopressin V(2)-like receptors in rat inner medullary collecting duct cells. The vasopressin V(1B) receptor-selective agonist [deamino-Cys(1), D-3-(Pyridyl)-Ala(2), Arg(8)]vasopressin (D3PVP) did not stimulate the [Ca(2+)](i) increase in high-density vasopressin V(2) receptor-expressing CHO cells, but did in inner medullary collecting duct cells. Moreover, the vasopressin V(1A)/V(2) receptor dual antagonist 4'-[(2-methyl-1,4,5,6-tetrahydroimidazo[4,5-d][1] benzazepin-6-yl)carbonyl] 2-phenylbenzanilide (YM087), which has no effect on vasopressin V(1B) receptors, did not block the [Ca(2+)](i) increase in inner medullary collecting duct cells when stimulated by dDAVP and D3PVP. On reverse transcription-polymerase chain reaction (RT-PCR) analysis of kidney, vasopressin V(1B) receptor mRNA was detected only in the medulla. We propose that the true nature of the vasopressin V(2)-like receptor in the inner medullary collecting duct is the vasopressin V(1B) receptor, rather than the vasopressin V(2) receptor expressed at high-density.
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PMID:Evidence that atypical vasopressin V(2) receptor in inner medulla of kidney is V(1B) receptor. 1093 86

The neonatal Fc receptor, FcRn, transports immunoglobulin G across intestinal cells in suckling rats. FcRn enters these cells by endocytosis and is present on the apical and basolateral surfaces. We investigated the roles of aromatic amino acids and a dileucine motif in the cytoplasmic domain of rat FcRn. We expressed mutant FcRn in which alanine replaced Trp-311, Leu-322, and Leu-323, or Phe-340 in the inner medullary collecting duct cell line IMCD. Individual replacement of the aromatic amino acids or the dileucine motif only partially blocked endocytosis of (125)I-Fc, whereas uptake by FcRn containing alanine residues in place of both Trp-311 and the dileucine motif was reduced to the level obtained with the tailless receptor. Leu-314 was required for the function of the tryptophan-based endocytosis signal, and Asp-317 and Asp-318 were required for the dileucine-based signal. Nonvectorial delivery of newly synthesized FcRn to the two cell surfaces was unaffected by loss of the endocytosis signals. However, the steady-state distribution of endocytosis mutants was predominantly apical, unlike wild-type FcRn, which was predominantly basolateral. This shift appeared to arise because the loss of endocytosis signals inhibited apical to basolateral transcytosis of FcRn more than basolateral to apical transcytosis.
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PMID:Tryptophan- and dileucine-based endocytosis signals in the neonatal Fc receptor. 1109 78

Urinary excretion of renal brush border enzymes may serve as an early marker of renal injury. However, the distinction between physiological and pathological levels remains controversial, since enzymuria is affected by physiological parameters. To clarify the influence of diuresis, we investigated the urinary excretion of alanine-aminopeptidase (AAP; EC 3.4.11.2) as function of diuretic state. 17 healthy volunteers of both sexes were subjected to protocols with sudden or prolonged water load preceded and followed by a thirst period. Urinary excretion of AAP was measured using an enzyme kinetic assay. As expected AAP excretion increased with urine flow, the increments diminished yielding an overall excretion pattern that resembled saturation kinetics. This function is described by a mathematical model. This model assumes, that AAP is released in proximal tubules at a constant rate and reabsorbed or inactivated in the distal tubule and collecting duct. Non-linear fits of the model equation to our data allowed two parameters, chi and mu, to be defined. Chi describes the rate of AAP release independent of urinary flow, and mu the ratio of distal tubular reabsorption or inactivation. If a substrate is not reabsorbed at all, mu approximates zero. Since mu fitted for AAP differed significantly from zero, this indicates reabsorption or inactivation of AAP in the distal nephron. Therefore, our study supports the theory of flow-dependent reabsorption or inactivation of AAP in the distal nephron.
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PMID:Influence of diuresis on enzymuria. 1149 53

The binding of mineralocorticoid hormones to the mineralocorticoid receptor is the first step in a cascade of events leading to the stimulation of Na(+) reabsorption by renal cortical collecting duct (CCD) principal cells. The agonist properties of mineralocorticoid hormones are linked to contacts between their 21-hydroxyl group and Asn770, a residue of the ligand-binding domain of the human mineralocorticoid receptor (hMR). Here, we investigate whether the presence of a hydroxyl group at position 11, 17, or 20 could also alter the activity of progesterone (P), a mineralocorticoid antagonist without the 21-hydroxyl group. Both 17 alpha-hydroxyprogesterone (17OHP) and 20 alpha-hydroxyprogesterone (20OHP) antagonized the aldosterone-induced trans-activation activity (IC(50): 17OHP, 10(-7) M; 20OHP, 10(-8) M) of the hMR transiently expressed in COS-7 cells lacking steroid receptors. In cultured mouse mpkCCD(cl4) principal cells, 17OHP and 20OHP also prevented the aldosterone-stimulated amiloride-sensitive component of the short-circuit current (Ams I(sc)), reflecting Na(+) absorption mediated by the epithelial Na(+) channel (ENaC). In contrast, 11 beta-hydroxyprogesterone (11OHP) activated the transiently expressed hMR in COS-7 cells in a dose-dependent manner (ED(50): 10(-8) M) and, like aldosterone, stimulated Ams I(sc) in mpkCCD(cl4) cells. Docking 11OHP within the hMR-ligand-binding domain homology model revealed that the agonist activity of 11OHP is caused by contacts between its 11 beta-hydroxyl group and Asn770. Furthermore, 11OHP was unable to activate the mutant hMR/N770A, in which Ala is substituted for Asn at position 770. These findings demonstrate that in the absence of the 21-hydroxyl group, the 11 beta-hydroxyl group can produce the contact with the hMR-Asn770 required for the hMR activation leading to stimulated Na(+) absorption.
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PMID:11beta-hydroxyprogesterone acts as a mineralocorticoid agonist in stimulating Na+ absorption in mammalian principal cortical collecting duct cells. 1243 97

Both mammals and birds can concentrate urine hyperosmotic to plasma via a countercurrent multiplier mechanism, although evolutionary lines leading to mammals and birds diverged at an early stage of tetrapod evolution. We reported earlier (Nishimura H, Koseki C, and Patel TB. Am J Physiol Regul Integr Comp Physiol 271: R1535-R1543, 1996) that arginine vasotocin (AVT; avian antidiuretic hormone) increases diffusional water permeability in the isolated, perfused medullary collecting duct (CD) of the quail kidney. In the present study, we have identified an aquaporin (AQP) 2 homolog water channel in the medullary cones of Japanese quail, Coturnix coturnix (qAQP2), by RT-PCR-based cloning techniques. A full-length cDNA contains an 822-bp open reading frame that encodes a 274-amino acid sequence with 75.5% identity to rat AQP2. The qAQP2 has six transmembrane domains, two asparagine-proline-alanine (NPA) sequences, and putative N-glycosylation (asparagine-124) and phosphorylation sites (serine-257) for cAMP-dependent protein kinase. qAQP2 is expressed in the membrane of Xenopus laevis oocytes and significantly increased its osmotic water permeability (P(f)), inhibitable (P < 0.01) by mercury chloride. qAQP2 mRNA (RT-PCR) was detected in the kidney; medullary mRNA levels were higher than cortical levels. qAQP2 protein that binds to rabbit anti-rat AQP2 antibody is present in the apical/subapical regions of both cortical and medullary CDs from normally hydrated quail, and the intensity of staining increased only in the medullary CDs after water deprivation or AVT treatment. The relative density of the approximately 29-kDa protein band detected by immunoblot from the medullary cones was modestly higher in water-deprived/AVT-treated quail. The results suggest that 1) medullary CDs of quail kidneys express a mercury-sensitive functioning qAQP2 water channel, and 2) qAQP2 is at least partly regulated by an AVT-dependent mechanism. This is the first clear identification of AQP2 homolog in nonmammalian vertebrates.
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PMID:Molecular and functional characterization of a vasotocin-sensitive aquaporin water channel in quail kidney. 1520 86

System L amino acid transporters mediate the movement of bulky neutral amino acids across cell membranes. Until now three proteins that induce system L activity have been identified: LAT1, LAT2, and LAT3. The former two proteins belong to the solute carrier family 7 (SLC7), whereas the latter belongs to SLC43. In the present study we present a new cDNA, designated LAT4, which also mediates system L activity when expressed in Xenopus laevis oocytes. Human LAT4 exhibits 57% identity to human LAT3. Like LAT3, the amino acid transport activity induced by LAT4 is sodium-, chloride- and pH-independent, is not trans-stimulated, and shows two kinetic components. The low affinity component of LAT4 induced activity is sensitive to the sulfhydryl-specific reagent N-ethylmaleimide but not that with high affinity. Mutation in LAT4 of the SLC43 conserved serine 297 to alanine abolishes sensitivity to N-ethylmaleimide. LAT4 activity is detected at the basolateral membrane of PCT kidney cells. In situ hybridization experiments show that LAT4 mRNA is restricted to the epithelial cells of the distal tubule and the collecting duct in the kidney. In the intestine, LAT4 is mainly present in the cells of the crypt.
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PMID:Identification of LAT4, a novel amino acid transporter with system L activity. 1565 99

The cell surface density of functional Kir1.1 (ROMK, KCNJ1) channels in the renal collecting duct is precisely regulated to maintain potassium balance. Here, we explore the mechanism by which phosphorylation of Kir1.1a serine 44 controls plasmalemma expression. Studies in Xenopus oocytes, expressing wild-type, phosphorylation mimic (S44D), or phosphorylation null (S44A) Kir1.1a, revealed that phosphorylation of serine 44 is required to stimulate traffic of newly synthesized channels to the plasma membrane through a brefeldin A-sensitive pathway. ROMK channels were found to acquire mature glycosylation in a serine 44 phosphorylation-dependent manner, consistent with a phosphorylation-dependent trafficking step within the endoplasmic reticulum/Golgi. Serine 44 neighbors a string of three "RXR" motifs, reminiscent of basic trafficking signals involved in directing early transport steps within the secretory pathway. Replacement of the arginine residues with alanine (R35A, R37A, R39A, R41A, or all Arg to Ala) did not restore cell surface expression of the phospho-null S44A channel, making it unlikely that phosphorylation abrogates a nearby RXR-type endoplasmic reticulum (ER) localization signal. Instead, analysis of the compound S44D phospho-mimic mutants revealed that the neighboring arginine residues are also necessary for cell surface expression, identifying a structure that determines export in the biosynthetic pathway. Suppressor mutations in a putative dibasic ER retention signal, located within the cytoplasmic C terminus (K370A, R371A), restored cell surface expression of the phospho-null S44A channel to levels exhibited by the phospho-mimic S44D channel. Taken together, these studies indicate that phosphorylation of Ser44 drives an export step within the secretory pathway to override an independent endoplasmic reticulum localization signal.
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PMID:A phosphorylation-dependent export structure in ROMK (Kir 1.1) channel overrides an endoplasmic reticulum localization signal. 1611 16


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