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)

It is widely accepted that in vivo the function of the papilla of the mammalian kidney is supported primarily by anaerobic metabolism. As a result, the major source of energy for support of function in the papilla is considered to be derived from glycolysis. This orientation originates from two concepts: 1) that in vivo the gaseous environment of the papilla has such a low PO2 that O2 availability limits O2 consumption, and 2) that papillary tissue has a high rate of glycolysis when compared with either cortical tissue or extrarenal tissues. It has also been tacitly assumed that papillary tissue has a "low" O2 uptake. Review of the measurements of PO2 of papillary tissue and of urine PO2 indicates that the PO2 of papillary tissue should not limit its aerobic mitochondrial oxidative metabolism. While the rate of aerobic glycolysis in papillary tissue is high, simultaneously papillary tissue has a rate of O2 uptake similar to that of liver and higher than that of muscle. The major (two-thirds) source of energy for papillary tissue in vitro is from O2 uptake. That papillary tissue is not exclusively dependent on glucose for its energy requirements is indicated by the greater stimulation of papillary tissue QO2 by succinate than by glucose. Thus, papillary tissue has both a high aerobic mitochondrial oxidative metabolism and a high aerobic glycolytic metabolism. It is suggested that the mechanism for the high rate of aerobic glycolysis in the presence of an adequate O2 supply is due to the relatively small mass of mitochondria in papillary tissue in relation to the amount of work done by the tissue. As a result of the limited rate of ATP production by the mitochondrial electron transport chain, the phosphorylation state ([ATP]/[ADP][Pi]) is reduced and the cytoplasmic redox state ([NAD+]/[NADH]) of the papillary collecting duct cells also becomes more reduced; changes in both ratios enhance the rate of glycolysis. This limited metabolic capacity of the collecting duct cells may permit an excess volume of solute and water to be excreted during volume expansion diuresis. The metabolic characteristics of the papilla, when compared to cortex, also provide a basis for the observed differences in substrate selectivity of cortex and medulla with respect to utilization of glucose and lactate. The experimental approaches that may provide information bearing on the suggested mechanisms for regulation of papillary metabolism in relation to tubular work functions are indicated.
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PMID:Is the function of the renal papilla coupled exclusively to an anaerobic pattern of metabolism? 22 Aug 81

11 beta-Hydroxysteroid dehydrogenase (11 beta-OHSD) transforms circulating glucocorticoids to their "biologically inert" 11-dehydro derivatives. Isoforms of 11 beta-OHSD with different cofactor requirements and biochemical properties [Michaelis constant (Km) and maximal velocity (Vmax)] exist in the kidney. Since epithelial cells derived from the toad bladder also contain this enzyme, we wished to further characterize its properties in prepared cell homogenates. 11 beta-OHSD from toad bladder demonstrated a clear preference for NAD+ over NADP+ as a cofactor similar to that observed in renal cortical collecting duct (CCD) cells. Furthermore, 11 beta-OHSD had a rapid onset of action. The apparent Km for corticosterone was 16.3 x 10(-8) M, a value comparable to that observed for enzyme from CCD, and a Vmax of 4.8 x 10(-12) mol.mg protein-1.min-1. The end product, 11-dehydrocorticosterone (compound A), influenced enzyme activity; it increased 11 beta-OHSD activity at corticosterone concentrations below the apparent Km for the enzyme and inhibited 11 beta-OHSD activity at corticosterone concentrations above the Km for the enzyme. The inhibitory effects of compound A appeared noncompetitive with an apparent equilibrium constant (Ki) of 2.8 x 10(-7) M. Consistent with its inhibitory action on 11 beta-OHSD, compound A (10(-6) M) enhanced the short-circuit current response to corticosterone (10(-7) M) in the intact toad bladder (experimental 2.03 +/- 0.33 vs. control 1.40 +/- 0.17 times above baseline; n = 7, P < 0.01). Thus 11 beta-OHSD in toad bladder resembles the isoform found in CCD, and compound A may be biologically important as a regulator of 11 beta-OHSD.
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PMID:Activity of 11 beta-hydroxysteroid dehydrogenase in toad bladder: effects of 11-dehydrocorticosterone. 849 39

Mineralocorticoid receptors in the inner medullary collecting duct (IMCD) are protected from glucocorticoid binding by an enzyme, 11 beta-hydroxysteroid dehydrogenase type 2 (11 beta-HSD2). To study the role of 11 beta-HSD2 in acid-base homeostasis, 11 beta-HSD2 activity was measured in rat IMCD-enriched cell suspensions. Homogenates of cell suspensions were incubated in buffers ranging in pH from 6.00 to 8.15 in the presence of 1 microCi of 3H-corticosterone (CS) and 400 microM NAD+. Enzyme activity was expressed as the amount of 3H-CS converted to 3H-11-dehydrocorticosterone (DHCS). IMCD 11 beta-HSD2 activity at pH 6.5 was 49% of activity at pH 7.5; 22.5 versus 11.0 fmol/microgram of protein per h. Experiments also were performed on intact cell suspensions at pH 7.5 and 6.5. There was a 42% inhibition in the IMCD cell suspension conversion rate of 3H-CS to 3H-11-DHCS at pH 6.5; 13.1 versus 7.6 fmol/microgram per h (P < 0.005). In cell suspensions at pH 7.5, 1-day acid loading caused a 26% inhibition in conversion rate, 13.2 versus 9.9 fmol/microgram per h (P < 0.05), when compared with controls. These results suggest that during acute metabolic acidosis, IMCD 11 beta-HSD2 is inhibited and may allow access to the mineralocorticoid receptors by glucocorticoids.
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PMID:Inhibition of IMCD 11 beta-hydroxysteroid dehydrogenase type 2 by low pH and acute acid loading. 1049 81

The kidney (11-HSD2 or 11-HSDK) isozyme of 11beta-hydroxysteroid dehydrogenase confers specificity for aldosterone on mineralocorticoid receptors in target tissues. In rodent kidney, this isozyme is expressed mainly in cortical collecting ducts and is undetectable in proximal tubules. Using mouse M-1 and rabbit RCD cortical collecting duct cells, we analyzed the 5'-flanking region of the human HSD11K gene encoding this enzyme in an attempt to identify transcriptional regulatory elements responsible for gene expression in the kidney. M-1 and RCD cells had high levels of NAD+ dependent 11-HSD activity with corticosterone as the substrate. Luciferase reporter constructs containing 1785 or 327 nucleotides (nt) upstream of the initiator ATG codon were expressed at similar levels in each cell line, but deletion to 167 nt almost completely abolished expression in both cell types. This region is GC-rich and contain Sp1 binding sites. Electrophoretic mobility shift assays of the region containing the putative Sp1 sites showed several DNA-protein complexes in both the cell types. Mutations of the Sp1 sites decreased transcriptional activity in M-1 cells; however, these mutations had a marginal effect in the RCD cells. These results suggest that elements controlling renal cell type expression are located in the proximal 327 nucleotides of the 5' flanking region of HSD11K.
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PMID:Expression of HSD11K (NAD+ dependent 11beta-hydroxysteroid dehydrogenase) promoter constructs in renal cell lines. 1092 54