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 C57BL/6J-cpk mouse has a form of autosomal-recessive polycystic kidney disease characterized by the rapid growth of large collecting duct cysts and the development of severe renal failure usually by three to four weeks of age. Previous studies had shown higher steady-state levels of proto-oncogene mRNA in these cystic kidneys. It is now shown using nuclear run-on transcription that the c-fos and c-myc proto-oncogenes are transcribed at higher rates in cystic kidneys, and thus that increased transcription, in part, may account for the increased mRNA levels. c-myc mRNA was detected by in situ hybridization in nephron anlagen and elongating tubules of normal and cystic kidneys during late fetal and early neonatal kidney development. Localization of c-myc expression in the normal kidney decreased with age over the three-week postnatal period. By contrast, c-myc mRNA was found in cysts as early as three days of age, with increased levels at two and three weeks. c-myc expression was also elevated in apparently normal, non-dividing proximal tubules in three-week-old cystic animals. On the basis of these findings, we suggest that c-myc expression is linked to the proliferation of cells engaged in the primary cystogenic process, and that expression of this gene in proximal tubule cells of severely azotemic animals reflects the compensatory response of residual tubular epithelial cells to progressive renal dysfunction.
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PMID:Localization of overexpressed c-myc mRNA in polycystic kidneys of the cpk mouse. 155 5

Endothelin-1 (ET-1) is produced by mesangial cells and potently regulates glomerular hemodynamics. The agents controlling mesangial cell ET-1 release are not well known; however, recent studies indicate that factors released during the inflammatory process can augment mesangial cell ET-1 production. One immune cell cytokine, tumor necrosis factor (TNF), is an important mediator of glomerular inflammation. Many of the renal effects of TNF are similar to those caused by ET-1, but the effect of TNF on mesangial cell ET-1 production is unknown. The current study examined the effect of TNF on ET-1 synthesis and release by mesangial cells. TNF, but not IL1, caused a dose-dependent and time-dependent increase in immunoreactive ET-1 in the supernatants of rat mesangial cells in culture. TNF augmentation of mesangial cell ET-1 release required at least 2 hours of exposure to a minimal concentration of 10 U/ml TNF. Blot hybridization analysis of mesangial cell RNA using a rat prepro-ET-1 cDNA revealed a 2.3 kb messenger RNA that was increased on exposure to TNF. The stimulatory effect of TNF on ET-1 release is not a general property of ET-1-producing cells because proximal tubule, medullary thick ascending limb, cortical collecting tubule, and inner medullary collecting duct cells did not increase ET-1 production on exposure to TNF. These data indicate that TNF is a potent stimulator of mesangial cell ET-1 production and raise the possibility that ET-1 could mediate, at least in part, renal dysfunction associated with high glomerular TNF levels.
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PMID:Production of endothelin-1 by rat mesangial cells: regulation by tumor necrosis factor. 158 97

Cells from the inner medullary collecting duct (IMCD) exhibit Na(+)-H+ exchange. The present studies were performed to address certain important characteristics of this process in cultured IMCD cells. First, Na(+)-H+ exchange was found to be present both at 37 degrees C and at 25 degrees C, in contrast to Na(+)-independent H+ extrusion, which was only observed in some cultures and only at 37 degrees C. Second, with the use of image analysis techniques, virtually all cells in IMCD cultures were demonstrated to possess Na(+)-H+ exchange, whether or not the cells exhibited Na(+)-independent intracellular pH recovery from acid loads. Also, Na(+)-H+ exchange was found to be expressed on the basolateral aspect of these cells, but not on the apical membrane. These properties of IMCD Na(+)-H+ exchange are consistent with a function to regulate intracellular pH rather than mediate transepithelial acid-base transport. Na(+)-H+ exchange in IMCD cells was also compared with that in cultured renal proximal tubule cells. Despite physiologically distinct roles in vivo, Na(+)-H+ exchange in these two cell types in culture was found to be similar with respect to the Km for Na+ and the Ki for 5-(N-ethyl-N-isopropyl)amiloride. These data are consistent with functionally similar (if not identical) processes mediating Na(+)-H+ exchange in these two cell types, but with opposite polarity.
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PMID:Inner medullary collecting duct Na(+)-H+ exchanger. 164 66

To examine the role of tubulointerstitial cell interaction in the regulation of fibroblast growth, fibroblasts from the rabbit renal cortex (CF) and papilla (PF) were cocultured with epithelial cells from the same tissue location. Inner medullary collecting duct epithelial cells (IMCDE) or IMCDE-conditioned medium stimulated DNA synthesis in PF, whereas proximal tubule epithelium (PTE) had no effect on the proliferation of CF. PF and CF showed a similar mitogenic response to exogenous epidermal growth factor and insulin-like growth factor 1 (IGF-I). Transforming growth factor-beta 1 inhibited growth of both cell types, and basic fibroblast growth factor (bFGF) had no effect on proliferation of either cell type. In contrast, platelet-derived growth factor (PDGF) was a potent mitogen for PF but was only weakly mitogenic for CF. Both CF and PF expressed a similar number of a single-affinity class of PDGF receptors (Kd, 2-4 x 10(-10) M). Assay for growth factor activity in conditioned medium from IMCDE and PTE showed that only IMCDE produced detectable PDGF. IMCDE-stimulated proliferation of PF was partially blocked by an antibody to PDGF, whereas antibodies to IGF-I had no neutralizing effect. The data suggest a role for PDGF in the regulation of interstitial fibroblast proliferation by IMCDE in the renal papilla. This paracrine system may be important in the pathogenesis of some forms of interstitial fibrosis of the kidney.
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PMID:Fibroblasts of rabbit kidney in culture. II. Paracrine stimulation of papillary fibroblasts by PDGF. 165 5

Renal cortical tubules consist of polarized epithelial cells where Na/H antiport activity has been demonstrated on the apical and/or basolateral membrane. Apical Na/H antiport activity plays an important role in transcellular bicarbonate (HCO3-) reabsorption, whereas basolateral Na/H antiport activity could be involved in transcellular HCO3- secretion as well as cell volume and pH control. To determine whether this heterogeneity in both localization and function is due to the existence of more than one Na/H antiporter, we studied the tissue distribution of Na/H antiporter mRNA by use of reverse transcription (RT) and polymerase chain reaction (PCR) in isolated nephron segments from rat renal cortex. The primers used were directed against the rat renal cortical Na/H antiporter cDNA which is homologous to the human growth factor-activatable Na/H antiporter. RT/PCR of beta-actin mRNA were performed as positive controls. Na/H antiporter mRNA expression in the proximal tubule was not detectable in S1 and S2 segments from superficial and most midcortical nephrons, which exhibit exclusively luminal Na/H antiport activity. It was expressed in S1 and S2 segments from juxtamedullary nephrons which have also basolateral Na/H antiport activity. Beta-actin mRNA was expressed uniformly in all segments of the proximal tubule. Na/H antiporter mRNA was also expressed in cortical thick ascending limb and cortical collecting duct, segments with basolateral Na/H antiport activity as well as in the glomeruli. In conclusion, at least two different Na/H antiporters exist in the renal cortex, i.e., the proximal tubule. The close correlation between functional localization of basolateral Na/H antiport activity and mRNA expression suggests that the rat kidney Na/H antiporter DNA homologous to the human growth factor activatable Na/H antiporter encodes a basolateral exchanger. The observed expression in a minority of midcortical proximal tubules could reflect a certain heterogeneity in these nephron segments.
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PMID:Na/H antiporter mRNA expression in single nephron segments of rat kidney cortex. 165 75

Growth hormone (GH) and insulin-like growth factor I (IGF-I) exert a variety of actions in renal tissue. To shed light upon the renal GH-IGF I axis we have characterized the cell biology of GH and IGF I in two parts of the nephron that are targets for these peptides, proximal tubule and collecting duct. Receptors for both GH and IGF I are present in the basolateral membrane of the renal proximal tubular cell. GH activates phospholipase C and IGF I stimulates phosphorylation of its receptor at this site. Both peptides directly enhance gluconeogenesis in proximal tubule. GH stimulates IGF I gene expression in collecting duct. IGF I of collecting duct origin could act as a paracrine growth factor in other portions of the nephron. IGF I may be causative of renal hypertrophy that occurs in the settings of hypersomatotropism, unilateral nephrectomy (compensatory hypertrophy) and diabetes mellitus.
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PMID:Renal cellular biology of growth hormone and insulin-like growth factor I. 165 79

The localization of membrane-bound gamma-glutamyltransferase with monoclonal antibody (mAb) 138H11 proved to be of value for differential diagnosis of renal cancer, since it correlated with the histogenetic profile of human epithelial renal tumors. Immunoreactive gamma-glutamyltransferase was located in the proximal tubule in all normal human kidneys (15/15) examined thus far by both ultrastructural and immunohistochemical techniques. From 68 epithelial renal cancers tested 31/31 clear-cell carcinomas and 15/16 chromophilic carcinomas expressed the target epitope of mAb 138H11. In contrast, 0/11 oncytomas, 0/9 chromophobic carcinomas, and 0/1 Duct-Bellini carcinoma were immunoreactive. These results support a model of histogenesis and classification of epithelial renal tumours, according to which clear-cell and chromophilic renal carcinomas originate from transformed proximal tubule cells, whereas oncocytomas, chromophilic and Duct-Bellini carcinomas originate from cells of the collecting duct.
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PMID:Differential diagnosis of histogenetically distinct human epithelial renal tumours with a monoclonal antibody against gamma-glutamyltransferase. 167 84

ICI 207,828 is a novel eukalemic diuretic in animals that is comparable in effect to hydrochlorothiazide. We used micropuncture and microperfusion techniques to determine the site(s) of action of this compound in the rat nephron. Either furosemide (FUR) or ICI 207,828 were perfused through the loop of Henle in situ. Both compounds caused significant reduction in water and electrolyte reabsorption by the loop. The effect of ICI 207,828 was significantly less than that of FUR. Both amiloride and ICI 207,828 were perfused, in situ, through the superficial distal tubule. ICI 207,828 had an effect similar to amiloride. Sodium and water reabsorption and potassium secretion were inhibited. In free-flow micropuncture studies, ICI 207,828, infused continuously i.v., had little effect on electrolyte and water reabsorption by the superficial proximal tubule. This compound significantly inhibited water and electrolyte reabsorption by the loop of Henle. Distal tubule secretion of potassium was inhibited. In addition, fractional potassium reabsorption beyond the superficial, late distal tubule was inhibited by ICI 207,828. From these results, we conclude that ICI 207,828 significantly inhibits electrolyte and water transport by the loop of Henle and distal tubule, and at sites beyond the superficial distal tubule such as either the collecting duct system or juxtamedullary nephrons. The reduction in distal potassium secretion, in concert with reduced loop of Henle and postdistal reabsorption, results in no net potassium loss in the urine, thus rendering this compound eukalemic.
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PMID:Evaluation of the renal site of action of a novel, eukalemic diuretic, ICI 207,828. 173 95

Two types of proton-translocating ATPases, H-ATPase and H-K-ATPase, are found in the renal tubular cells. H-ATPase is present in both endocytic vesicles and apical membranes in almost all nephron segments. On the other hand, H-K-ATPase is present only in the connecting tubule and collecting duct. There is evidence to suggest that H-ATPase may be involved in H secretion in almost all nephron segments. H-K-ATPase is involved not only in H secretion but also in K absorption in the collecting duct segments. Aldosterone administration and metabolic acidosis stimulate the activity of H-ATPase in all collecting duct segments, whereas hypokalemia has only a limited effect on H-ATPase activity. On the other hand, hypokalemia, as well as metabolic acidosis, stimulates H-K-ATPase activity in the collecting duct segments, whereas aldosterone administration alone plays a minor role in the regulation of this enzyme. The physiological role and regulation of H-ATPase in the proximal tubule has not been established.
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PMID:Respective roles of H-ATPase and H-K-ATPase in ion transport in the kidney. 183 66

Endothelins regulate nephron sodium and water transport, prostaglandin E2 (PGE2) synthesis, and phospholipid metabolism. Recent studies suggest that renal tubule cells synthesize endothelins. To determine which nephron sites have such potential, endothelin production by cells derived from different nephron segments was examined. Immunoreactive endothelin 1 (ET-1) and endothelin 3 (ET-3) were measured in supernatants of cultured rabbit proximal tubule (PT), medullary thick ascending limb (MTAL), cortical collecting tubule (CCT), and inner medullary collecting duct (IMCD) cells. All cell types released immunoreactive ET-1 and ET-3. However, the amounts of endothelin produced differed as follows: IMCD greater than MTAL greater than CCT much greater than PT for ET-1 and IMCD greater than MTAL = PT = CCT for ET-3; in all cases ET-1 much greater than ET-3. To confirm de novo ET-3 synthesis, IMCD cells were labeled with [35S]cysteine, and the supernatant was immunoprecipitated with anti-ET-3 antibody. Sample and standard ET-3 eluted at identical positions on high-performance liquid chromatographs, confirming de novo synthesis of ET-3 by cultured IMCD cells. These data raise the possibility of an important functional role for nephron-derived endothelin and, in particular, endothelin produced by tubule cells in the medulla.
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PMID:Endothelin synthesis by rabbit renal tubule cells. 187 47


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