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)

Circadian rhythms in the urinary excretion of eleven heavy metals and organic substances were examined under free, water-restrictive and water-loading conditions for 6 d (2 d for each of the three conditions) in twenty metal workers exposed to lead, zinc and copper. Circadian rhythms were found for all heavy metals and organic substances as well as for urinary flow (UF) rate, creatinine (Cn) and total urinary solutes (TUS). The Cn rhythm was significantly unparallel to the UF rhythm under the water-loading condition, indicating that the two rhythms were essentially different from each other. Circadian rhythms of the eleven urinary substances were then related to the Cn and UF rhythms, using profile analysis. The results indicated that the rhythms in the manganese, chromium, copper and beta-2-microglobulin excretion depend on the Cn rhythm, i.e. the rhythm of glomerular filtration; the rhythms in the hippuric acid, delta-aminolevulinic acid and TUS excretion are on the UF rhythm, i.e. the rhythm of reabsorption by the distal tubule and collecting duct. On the other hand, the rhythms in the lead, inorganic mercury, cadmium, zinc and coproporphyrin excretion were considered as reflecting complex renal excretory mechanisms.
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PMID:Circadian rhythms in the urinary excretion of heavy metals and organic substances in metal workers in relation to renal excretory mechanism: profile analysis. 335 May 98

Circadian rhythms in the urinary excretion of metals and organic substances were examined in ten "healthy" men under conditions of water loading and restriction. Four characteristic rhythms were observed: (1) decreased excretion during the night for lead and urinary flow rate; (2) decreased excretion of hippuric acid, delta-aminolevulinic acid, coproporphyrin, creatinine, and total urinary solutes during the night and morning hours; (3) increased excretion of mercury and zinc during the morning hours; and (4) no significant variation for copper. Excretion of lead, hippuric acid, delta-aminolevulinic acid, and total urinary solutes was significantly correlated with urinary flow rate and creatinine excretion, which suggested that their circadian rhythms were the consequence of reduced glomerular filtration and increased reabsorption by the distal tubule and collecting duct during the night and morning hours. Similarly, it was suggested that the mercury and zinc rhythms resulted partly from increased reabsorption during the night hours; the coproporphyrin rhythm reflected reduced glomerular filtration of coproporphyrinogen during the night and morning hours.
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PMID:Circadian rhythms in the urinary excretion of metals and organic substances in "healthy" men. 666 37

Carbonic anhydrase is a zinc metalloenzyme widely distributed throughout the tissues of the body. This enzyme exists in a number of isozymic forms in most mammalian species. Significant advances over the past decade have been made in characterizing the nature of renal carbonic anhydrase. In the kidney, this enzyme is thought to play a pivotal role in urinary acidification and bicarbonate reabsorption. Two distinct isozymes of carbonic anhydrase have now been identified in the mammalian kidney. A soluble cytoplasmic form, similar if not identical to human erythrocyte carbonic anhydrase C, accounts for the bulk of the renal carbonic anhydrase activity. In addition, a membrane-bound form constituting only about 2--5% of the renal activity has been found in the brush border and basolateral fractions of kidney homogenates. The histochemical and immunocytochemical localization of these isozymes along the nephron and collecting duct system of various mammalian species suggests that marked heterogeneity exists. The Editorial Review examines the biochemical and morphological approaches that have been used to elucidate the nature of renal carbonic anhydrase and to assess its distribution along the urinary tubule. Possible physiological roles for the renal carbonic anhydrases are considered for the different segments of the nephron and collecting duct system.
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PMID:Renal carbonic anhydrase. 681 35

The renal carbonic anhydrases, CA II (cytosolic) and CA IV (membrane bound), are believed to facilitate renal acid secretion. We have recently shown that renal cortical sodium dodecyl sulfate (SDS)-resistant hydratase (presumably CA IV) activity was stimulated 241% during chronic metabolic acidosis (CMA). In the present study, we examined the expression and regulation of CA IV mRNA in kidneys from control and acidotic rabbits. To obtain a CA IV probe, we reverse transcribed rabbit kidney total RNA and amplified a approximately 780-base pair (bp) DNA product using primers derived from the human CA IV sequence. Using this product, we screened one-half of a kidney cortex cDNA library and sequenced a 1,194-bp cDNA, which contained the entire open-reading frame of rabbit CA IV. The cDNA was 78% identical to human and 71% to rat CA IV. The deduced amino acid sequence projected an active zinc binding site and two glycosylation sites. Northern analysis yielded a single transcript of approximately 1,600 bp in size expressed more abundantly in cortex and inner medulla than in outer medulla. CA IV mRNA was also expressed abundantly in lung but not in liver or spleen. The high abundance of CA IV mRNA in inner medulla was localized by in situ hybridization to medullary collecting duct cells. Rabbits exposed to CMA showed significant upregulation of CA IV mRNA expression in kidney cortex and outer medulla. Despite a numerical increase, excessive variability precluded statistical significance in the inner medulla. Thus CA IV mRNA was expressed abundantly in kidney and stimulated by CMA, similar to what has been previously observed for SDS-resistant hydratase (presumed CA IV) activity. It is likely that the regulation of CA IV mRNA and activity is relevant to the kidney's adaptation to CMA.
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PMID:Expression of carbonic anhydrase IV mRNA in rabbit kidney: stimulation by metabolic acidosis. 914 58

1. In vivo microinjections of 55FeCl3 were made to assess renal iron (Fe2+/3+) transport in the anaesthetized rat. 2. Following microinjection into proximal convoluted tubules (PCTs), 18.5 +/- 2.9 % (mean +/- s.e.m., n = 11) of the 55Fe was recovered in the urine. This recovery was not dependent on the injection site indicating that iron is not reabsorbed across the surface convolutions of the proximal tubule. 3. Following microinjection into distal convoluted tubules (DCTs) 46.1 +/- 6.1 % (n = 8) of the injected 55Fe was recovered. Taken together the recovery data from the PCT and DCT microinjection studies indicate that the transport of iron occurs in the loop of Henle (LH) and collecting duct system. 4. In vivo luminal microperfusion was used to examine iron transport by the LH in more detail. In tubules perfused with 7 micromol l-1 55FeCl3, 52.7 +/- 8. 3 % (n = 8) of the perfused 55Fe was recovered in the collected fluid, indicating significant iron reabsorption in the LH. Addition of copper (Cu2+ as 7 micromol l-1 CuSO4), manganese (Mn2+ as 7 micromol l-1 MnSO4) or zinc (Zn2+ as 7 micromol l-1 ZnSO4) to the perfusate did not affect reabsorption of water, Na+ or K+, but increased recovery of 55Fe to 83.5 +/- 6.8 % (n = 8, P < 0.04), 75.8 +/- 5.9 (n = 6, not significant, n.s.) and 67.9 +/- 3.8; (n = 9, n.s. ), respectively. 5. Thus, iron transport in the LH can be reduced by the addition of copper or manganese to the luminal perfusate suggesting that these ions may compete with iron for a common transport pathway. However, this pathway may not be shared by zinc.
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PMID:In vivo characterization of renal iron transport in the anaesthetized rat. 1076 35

Epithelial cells derived from the mammalian kidney medulla are responsive to urea at the levels of signal transduction and gene regulation. Hybridization of RNA harvested from control- and urea-treated murine inner medullary collecting duct (mIMCD3) cells with a cDNA expression array encoding stress-responsive genes suggested that heme oxygenase (HO)-1 mRNA was upregulated by urea. RNase protection assay confirmed this upregulation; hypertonicity also increased HO-1 mRNA expression but neither hypertonic NaCl nor urea were effective in the nonrenal 3T3 cell line. The effect on HO-1 expression appeared to be transcriptionally mediated on the basis of mRNA half-life studies and reporter gene analyses using the promoters of both human and chicken HO-1. Although urea signaling resembles that of heavy metal signaling in other contexts, the effect of urea on HO-1 transcription was independent of the cadmium response element in this promoter. Urea-inducible HO-1 expression was sensitive to antioxidants but not to scavengers of nitric oxide. Urea also upregulated HO-1 protein expression and pharmacological inhibition of HO-1 action with zinc protoporphyrin-sensitized mIMCD3 cells to the adverse effects of hypertonicity but not to urea. Coupled with the prior observation of others that HO-1 expression increases along the renal corticomedullary gradient, these data suggest that HO-1 expression may comprise an element of the adaptive response to hypertonicity and/or urea in renal epithelial cells.
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PMID:Urea and hypertonicity increase expression of heme oxygenase-1 in murine renal medullary cells. 1159 56

Ammonia stimulates cortical collecting duct (CCD) net bicarbonate reabsorption by activating an apical H(+)-K(+)-ATPase through mechanisms that are independent of ammonia's known effects on intracellular pH and active sodium transport. The present studies examined whether this stimulation occurs through soluble N-ethylmaleimide-sensitive fusion attachment receptor (SNARE) protein-mediated vesicle fusion. Rabbit CCD segments were studied using in vitro microperfusion, and transepithelial bicarbonate transport was measured using microcalorimetry. Ammonia's stimulation of bicarbonate reabsorption was blocked by either chelating intracellular calcium with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid acetoxymethyl ester or by inhibiting microtubule polymerization with colchicine compared with parallel studies performed in the absence of these inhibitors. An inactive structural analog of colchicine, lumicolchicine, did not alter ammonia's stimulation of bicarbonate reabsorption. Tetanus toxin, a zinc endopeptidase specific for vesicle-associated SNARE (v-SNARE) proteins, prevented ammonia from stimulating net bicarbonate reabsorption. Consistent with the functional evidence for v-SNARE involvement, antibodies directed against a conserved region of isoforms 1-3 of the tetanus toxin-sensitive, vesicle-associated membrane protein (VAMP) members of v-SNARE proteins labeled the apical and subapical region of collecting duct intercalated cells. Similarly, antibodies to NSF protein, a protein involved in activation of SNARE proteins for subsequent vesicle fusion, localized to the apical and subapical region of collecting duct intercalated cells. These results indicate that ammonia stimulates CCD bicarbonate reabsorption through an intracellular calcium-dependent, microtubule-dependent, and v-SNARE-dependent mechanism that appears to involve insertion of cytoplasmic vesicles into the apical plasma membrane of CCD intercalated cells.
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PMID:Mechanisms through which ammonia regulates cortical collecting duct net proton secretion. 1199 29

We have used the perforated patch clamp and fura-2 fluorescence techniques to study the effect of extracellular Zn(2+) on whole-cell Ca(2+)-activated Cl(-) currents (I (CLCA)) in mouse inner medullary collecting duct cells (mIMCD-3). I (CLCA) was spontaneously active in 74% of cells under basal conditions and displayed time and voltage-independent kinetics and an outwardly rectifying current/voltage relationship (I/V). Addition of zinc chloride (10-400 microM) to the bathing solution resulted in a dose-dependent increase in I (CLCA) with little change in Cl(-) selectivity or biophysical characteristics, whereas gadolinium chloride (30 microM) and lanthanum chloride (100 microM) had no significant effect on the whole-cell current. Using fura-2-loaded mIMCD-3 cells, extracellular Zn(2+) (400 microM) stimulated an increase in intracellular Ca(2+) to an elevated plateau. The Zn(2+)-stimulated [Ca(2+)](i) increase was inhibited by thapsigargin (200 nM), the IP(3) receptor antagonist 2-aminoethoxydiphenyl borate (10 microM) and removal of bath Ca(2+). Pre-exposure to Zn(2+) (400 microM) markedly attenuated the ATP (100 microM)-stimulated [Ca(2+)](i) increase. These data are consistent with the hypothesis that extracellular Zn(2+) stimulates an increase in [Ca(2+)](i) by a release of calcium from thapsigargin/IP(3) sensitive stores. A possible physiological role for a divalent metal ion receptor, distinct from the extracellular Ca(2+)-sensing receptor, in IMCD cells is discussed.
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PMID:Extracellular zinc stimulates a calcium-activated chloride conductance through mobilisation of intracellular calcium in renal inner medullary collecting duct cells. 1702 97

GATA3 is a zinc-finger transcription factor, which is expressed in various normal and neoplastic tissues. Amongst tumors, it labels urothelial carcinoma, collecting duct carcinoma of the kidney, breast carcinoma, lymphoma and, uncommonly, endometrial carcinoma. Few studies have investigated its positivity in various neoplasms that may mimic urothelial neoplasms. In this study, we evaluated GATA3 expression in urinary bladder paragangliomas, which may closely mimic urothelial carcinomas. We retrieved 12 cases of paragangliomas from the urinary bladder and 20 cases of paragangliomas from non-urologic sites using the Hopkins Pathology Data Base system. GATA3 was positive in 10 of the 12 (83%) urinary bladder paragangliomas studied on routine slide sections. Most (6/12) of the staining was diffusely strong (3+) staining, whereas the rest (4/12) that were positive showed mixed intensities (strong 3+ to moderate 2+). The 20 paragangliomas from other sites were constructed into tissue microarrays, wherein three cores from each tumor were taken. Fifteen out of 20 (75%) paragangliomas outside of the bladder were positive for GATA3 staining. Moderate (2+) or strong (3+) staining was seen in 13/20 (65%) of extravesical paragangliomas, ranging from 5 to 100% of the cell labeling (mean 59%, median 60%). In the remaining 7/20 (35%) cases, only weak (2/7) or negative (5/7) immunoreactivity for GATA3 was seen. An additional 15 cases of metastatic paraganglioma from various primary sites were retrieved with 12 of 15 (80%) metastatic paragangliomas staining positively for GATA3. Overall, for paragangliomas, regardless of site, 78.7% were positive for GATA3. Recognition of this finding will aid pathologists in preventing a misdiagnosis of a urothelial tumor based on GATA3 expression, which is critical given the differences in treatment, follow-up and prognosis between bladder paragangliomas and urothelial carcinoma.
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PMID:GATA3 expression in paragangliomas: a pitfall potentially leading to misdiagnosis of urothelial carcinoma. 2359 57

Zinc (Zn2+) is the second most abundant trace element, but is considered a micronutrient, as it is a cofactor for many enzymes and transcription factors. Whereas Zn2+ deficiency can cause cognitive immune or metabolic dysfunction and infertility, excess Zn2+ is nephrotoxic. As for other ions and solutes, Zn2+ is moved into and out of cells by specific membrane transporters: ZnT, Zip, and NRAMP/DMT proteins. ZIP10 is reported to be localized at the apical membrane of renal proximal tubules in rats, where it is believed to play a role in Zn2+ import. Renal regulation of Zn2+ is of particular interest in light of growing evidence that Zn2+ may play a role in kidney stone formation. The objective of this study was to show that ZIP10 homologs transport Zn2+, as well as ZIP10, kidney localization across species. We cloned ZIP10 from dog, human, and Drosophila ( CG10006), tested clones for Zn2+ uptake in Xenopus oocytes and localized the protein in renal structures. CG10006, rather than foi (fear-of-intimacy, CG6817) is the primary ZIP10 homolog found in Drosophila Malpighian tubules. The ZIP10 antibody recognizes recombinant dog, human, and Drosophila ZIP10 proteins. Immunohistochemistry reveals that ZIP10 in higher mammals is found not only in the proximal tubule, but also in the collecting duct system. These ZIP10 proteins show Zn2+ transport. Together, these studies reveal ZIP10 kidney localization, a role in renal Zn2+ transport, and indicates that CG10006 is a Drosophila homolog of ZIP10.
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PMID:Cloning, function, and localization of human, canine, and Drosophila ZIP10 (SLC39A10), a Zn2+ transporter. 3052 Jun 57


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