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)

Angiotensin II (Ang II)-mediated hypertension induces vascular smooth muscle cell hypertrophy and hyperplasia in systemic blood vessels, but the effects of Ang II on the intrinsic cell populations within the kidney have been less well characterized. We infused Ang II for 14 days into rats by minipump at doses (200 ng/min) that resulted in moderate hypertension (mean systolic blood pressure 156-172 mm Hg). Small renal arterial vessels of Ang II-infused rats demonstrated focal injury with fibrinoid necrosis and medial hyperplasia, whereas the glomerular capillaries demonstrated only rare segmental hyalinosis. Proliferation of vascular smooth muscle cells was pronounced (fourfold to 20-fold increase in [3H]thymidine incorporation) as opposed to a minimal proliferation of glomerular cells in Ang II-infused rats. In contrast, the principal effect of Ang II in glomeruli was to increase the expression of alpha-smooth muscle actin by mesangial cells and desmin by visceral glomerular epithelial cells. Ang II-infused rats also developed focal tubulointerstitial injury, with tubular atrophy and dilation, cast formation, an interstitial monocytic infiltrate, and mild interstitial fibrosis with increased type IV collagen deposition. The injury was associated with a proliferation of distal tubule, collecting duct, and interstitial cells as determined by immunostaining for proliferating cell nuclear antigen, and was accompanied by an increase in platelet-derived growth factor B-chain messenger RNA in the area of interstitial injury as localized by in situ hybridization. Renal interstitial cells also underwent phenotypic modulation in which they expressed alpha-smooth muscle actin. Vehicle-infused control rats displayed no tubular injury, proliferation, or phenotypic modulation. Thus, Ang II in doses that cause moderate hypertension induces marked vascular, glomerular, and tubulointerstitial injury with cell proliferation, leukocyte recruitment, phenotypic modulation with the upregulation of proteins normally associated with smooth muscle cells, and interstitial fibrosis.
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PMID:Renal injury from angiotensin II-mediated hypertension. 156 65

A cortical collecting duct (CCD) cell line has been developed from a mouse transgenic for the early region of simian virus 40, Tg(SV40E)Bri/7. CCDs were microdissected and placed on collagen gels. Monolayers were subsequently subcultured onto permeable collagen membranes and maintained in serum-supplemented medium. One line, designated M-1, retained many characteristics of the CCD, including a typical epithelial appearance and CCD-specific antigens. M-1 cells, when grown in monolayers on permeable supports, exhibited a high transepithelial resistance (885.7 +/- 109.6 ohms/cm2) and developed a lumen negative transepithelial potential difference (PD) of -45.7 +/- 3.5 mV. The associated short-circuit current (SCC) averaged 71.8 +/- 10.3 microA/cm2, and was reduced by 95% by luminal application of amiloride. The cultured cells responded to arginine vasopressin (AVP) with a significant increase in SCC. M-1 cells generated significant transepithelial solute gradients. After 24 hours incubation, the composition of the luminal (L) and basolateral (B) media (in mM) was: [Na+], L = 106.7 +/- 0.9 and B = 127.4 +/- 0.4; [K+], L = 8.6 +/- 0.6 and B = 2.1 +/- 0.3; [Cl], L = 68.6 +/- 5.8 and B = 101.8 +/- 6.6; [HCO3], L = 15.5 +/- 1.5 and B = 8.6 +/- 1.2; while pH was 7.16 +/- 0.03 at the luminal and 6.94 +/- 0.03 at the basolateral side. The formation of these concentration gradients indicates that the CCD cultures absorb Na+ and Cl- and secrete K+.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Characterization of a mouse cortical collecting duct cell line. 165 78

The inner medullary collecting duct (IMCD) is an important site of action for arginine vasopressin (AVP). To examine the mode of action of AVP in this segment, we measured the change in transepithelial resistance of cultured rat IMCD cells grown to confluence on collagen-coated Millicell culture plate inserts in response to AVP. Resistance was measured by use of an EVOM voltage-ohm meter. AVP at 10(-11)-10(-8) M caused a fall in resistance of 6.9 +/- 1.3 to 14.0 +/- 1.4 omega.cm2 (P less than 0.05 to less than 0.01 vs. no AVP), which was reversed by removal of AVP or addition of 10(-6) M amiloride. Pretreating the apical surface of IMCD cells with trypsin had no effect on resistance but totally prevented the antidiuretic hormone-induced fall in resistance. Pretreating the apical surface with trypsin and amiloride did not prevent the fall in resistance to AVP. Addition of 10(-9) M AVP or 10(-6) M forskolin increased 2-min adenosine 3',5'-cyclic monophosphate (cAMP) accumulation by 55 or 96%, respectively. Stimulation of endogenous cAMP accumulation by forskolin or the addition of exogenous 8-bromo-cAMP caused no change in resistance. To examine the relationship between intracellular calcium [( Ca2+]i) and AVP action, the response of [Ca2+]i to AVP was measured by use of fura-2. AVP induced no change in [Ca2+]i in IMCD cells in suspension, on glass cover slips, or on permeable supports. Ionomycin (25 nM) increased [Ca2+]i in IMCD cells and lowered resistance across monolayers, but the fall in resistance was not blocked by amiloride.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:AVP reduces transepithelial resistance across IMCD cell monolayers. 169 8

We evaluated the characteristics of renal lesions in rat autosomal recessive polycystic kidney (ARPK). In rat ARPK, small cysts appeared primarily in the medulla 2 months after birth and gradually extended to the cortex, forming large cysts involving the entire layer after 8 months. By immunofluorescence microscopy, type IV collagen was more strongly stained in the epithelial basement membrane of the rat ARPK than in the normal rat tubular basement membrane (TBM). Electron microscopy demonstrated a marked thickening, slight splitting and lamination of the TBM in the ARPK. As peroxidase-labeled lectins, dolichos biflorus very strongly stained the cyst epithelium whereas lens culinaris did not. These findings indicate that cysts in rat ARPK originate in the collecting duct.
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PMID:Autosomal recessive polycystic kidney in rats. 172 66

The distal inner medullary collecting duct (IMCD) is critical in the urinary concentrating process, in part because it is the site of vasopressin (AVP)-regulated permeability to urea. The purpose of these experiments was to develop a cell culture model of the IMCD on permeable structure and to characterize the responsiveness to AVP. Rat IMCD cells were grown to confluence on collagen-coated Millipore filters glued onto plastic rings. To assess the time required to achieve confluence, the transepithelial resistance was measured periodically and was found to be stable after 2 weeks, at a maximal value of 595 +/- 22 omega cm2. In separate monolayers the effect of AVP on inulin and urea permeability was determined. While inulin permeability was unchanged after AVP, urea permeability increased from 6.0 +/- 0.4 to peak values of 16.0 +/- 3.8 (10 nM), 23.1 +/- 3.9 (1 microM) and 28.1 +/- 4.9 (10 microM) x 10(-6) cm s-1 (n = 24). In 10 other monolayers, after the addition of 1 mM 8-Br-cAMP, urea permeability increased from 5.1 +/- 0.3 to 8.1 +/- 1.6 x 10(-6) cm s-1 and, after 8-Br-cAMP + 3-isobutyl-1-methylxanthine, to 12.2 +/- 0.7 x 10(-6) cm s-1. We conclude that rat IMCD cells grown in culture exhibit the characteristics of a 'tight' epithelium. Inulin and urea permeability are not different in the absence of AVP, consistent with high resistance junctional complexes. Furthermore, IMCD cells retain the capacity for AVP-regulated urea permeability, a characteristic feature of this nephron segment in vivo.
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PMID:Vasopressin-enhanced urea transport by rat inner medullary collecting duct cells in culture. 224 45

Thin cortical kidney explants from newborn New Zealand rabbits were cultured in Dulbecco's MEM containing 10% fetal bovine serum. Within 24 h the explants formed globular bodies which were completely covered by a monolayered epithelium. The cells show polar differentiation and resemble the renal collecting duct epithelium. By culturing the globular bodies in Dulbecco's MEM with D-valine instead of L-valine additionally a monolayer of renal collecting duct cells was obtained. For the study of glycoprotein synthesis the globular bodies and the collecting duct monolayers were incubated with various labelled carbohydrates, protein and collagen precursors and then fractionated into coarse membrane pellets. The synthesized glycoproteins were regained in 600 x g and 12,000 x g coarse membrane fractions and extracted with Triton X 100 buffer for column chromatography and SDS-polyacrylamide electrophoresis in 6 M urea. In addition to a 85,000 d glycoprotein, a carbohydrate rich collagen like protein (apparent molecular weight in column chromatography 200,000 d, in the SDS-polyacrylamide electrophoresis 150,000 d) was found. The 150,000 d glycoprotein incorporates favorably radioactive proline, sulfate, and smaller amounts of lysine, and leucine. Compared to the 85,000 d glycoprotein a double amount of glucosamine and galactose and four fold amount of fucose was detected. The 85,000 d protein has to be ascribed as a usual glycoprotein, in contrast the 150,000 d protein shows an unusual combination of characteristics and has to be considered as a new type of renal glycoprotein.
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PMID:Cell associated glycoproteins synthesized by cultured renal tubular cells. 717 68

The association of hepatocyte growth factor (HGF) with its high-affinity receptor, c-met, has been shown to induce mitogenesis, motogenesis, and morphogenesis in renal epithelial cells (L. G. Cantley, E. J. G. Barros, M. Gandhi, M. Rauchman, and S. K. Nigam. Am. J. Physiol. 267 (Renal Fluid Electrolyte Physiol. 36): F271-F280, 1994), suggesting that HGF may be critical to the orchestration of both renal development and regeneration following injury. Although signal transduction pathways activated by c-met include the phosphatidylinositol 3-kinase (PI-3-kinase), phospholipase C gamma, ras, and others, the activation of PI-3-kinase has been the most striking in vivo. We therefore investigated whether the pathways that mediate phenotypic changes in inner medullary collecting duct cells are altered by inhibition of PI-3-kinase with the fungal metabolite, wortmannin. In these cells, the mean inhibitory concentration for in vitro wortmannin inhibition of PI-3-kinase was approximately 0.2 nM. At this low concentration, motogenesis (quantified by chemotaxis) and morphogenesis (by branching-process formation within collagen matrix) were inhibited in a striking and parallel fashion, while mitogenesis was inhibited to a lesser degree. These experiments suggest that activation of PI-3-kinase is critical for c-met-mediated chemotaxis and tubulogenesis.
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PMID:HGF-mediated chemotaxis and tubulogenesis require activation of the phosphatidylinositol 3-kinase. 761 61

At least two kidney epithelial cell lines, the Madin-Darby canine kidney (MDCK) and the murine inner medullary collecting duct line mIMCD-3, can be induced to form branching tubular structures when cultured with hepatocyte growth factor (HGF) plus serum in collagen I gels. In our studies, whereas MDCK cells remained unable to form tubules in the presence of serum alone, mIMCD-3 cells formed impressive branching tubular structures with apparent lumens, suggesting the existence of specific factors in serum that are tubulogenic for mIMCD-3 cells but not for MDCK cells. Since normal serum does not contain enough HGF to induce tubulogenesis, these factors appeared to be substances other than HGF. This was also suggested by another observation: when MDCK cells or mIMCD-3 cells were cocultured under serum-free conditions with the embryonic kidney, both cell types formed branching tubular structures similar to those induced by HGF; however, only in the case of MDCK cells could this be inhibited by neutralizing antibodies against HGF. Thus, the embryonic kidney produces growth factors other than HGF capable of inducing tubule formation in the mIMCD-3 cells. Of a number of growth factors examined, transforming growth factor alpha (TGF-alpha) and epidermal growth factor (EGF) were found to be tubulogenic for mIMCD-3 cells. Whereas only HGF was a potent tubulogenic factor for MDCK cells, HGF, TGF-alpha, and EGF were potent tubulogenic factors for mIMCD-3 cells. Nevertheless, there were marked differences in the capacity of these tubulogenic factors to induce tubulation as well as branching events in those tubules that did form (HGF >> TGF-alpha > EGF). Thus, at least three different growth factors can induce tubulogenesis and branching in a specific epithelial cell in vitro (though to different degrees), and different epithelial cells that are capable of forming branching tubular structures demonstrate vastly different responses to tubulogenic growth factors. The results are discussed in the context of branching morphogenesis during epithelial tissue development.
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PMID:Differential tubulogenic and branching morphogenetic activities of growth factors: implications for epithelial tissue development. 775 20

Ca(2+)-activated K+ channels play an important role in Ca2+ signal transduction and may be regulated by mechanisms other than a direct effect of Ca2+. Inside-out patches of the apical membrane of confluent transformed rabbit cortical collecting duct cells cultured on collagen were subjected to patch clamp analysis. Two types of K+ channel, of medium and high conductance, were observed. The latter channel was characterized by a K+/Na+ permeability ratio of 10, an inwardly rectified current, a conductance of 80 pS at 0 mV, and an open probability dependent on both voltage and Ca2+. Guanosine 5'-triphosphate (GTP) but not a guanosine 5'-diphosphate (GDP) analogue, adenosine 5'-triphosphate (ATP), cytidine 5'-triphosphate (CTP), or inosine 5'-triphosphate (ITP), inhibited the activity of this Ca(2+)-activated K+ channel. The inhibitory effect of GTP was dose dependent, with a 50% inhibitory concentration of 10(-5) M in the absence of Mg2+. In the presence of Mg2+ (1 mM), which is required for the binding of GTP to G proteins, the 50% inhibitory concentration decreased to 3 x 10(-12) M. Pertussis toxin or cholera toxin (each at 10 ng/ml) did not prevent the inhibitory effect of GTP. After removal of GTP from the medium bathing an inhibited channel, subsequent application of Ca2+ failed to activate the channel. Ca(2+)-activated K+ channels of smooth muscle cells and proximal tubule cells did not respond to GTP. Thus, the Ca(2+)-activated K+ channel in the apical membrane of collecting duct cells is inhibited by GTP, which appears to exert its effect via a G protein that is insensitive to both cholera and pertussis toxins.
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PMID:Regulation by GTP of a Ca(2+)-activated K+ channel in the apical membrane of rabbit cortical collecting duct cells. 796 44

Previous experiments have shown that epithelial cells in the renal medulla produce endothelin-1 (ET-1) and possess ETB receptors. It has been suggested that medullary ET-1 may affect water and sodium absorption along the collecting ducts in an autocrine fashion. To study possible mechanisms responsible for the regulation of medullary ET-1 production, experiments were performed in M-1 cells and mIMCD-K2 cells, cell lines derived from cortical and inner medullary collecting ducts of SV40 transgenic mice, grown to confluence on collagen-coated filter inserts. Both cell lines were found to express ET-1 mRNA and to secrete ET almost exclusively into the basolateral medium as long as the transepithelial resistance was high. Inhibition of transcription with actinomycin D was followed by a decline in both ET mRNA [halftime (t1/2) = 30 min] and ET secretion (t1/2 = approximately 90 min). The addition of arginine vasopressin (AVP, 10(-8) M; 2- or 4-h exposure) or incubation of M-1 cells in hypertonic media (+50 mM NaCl, 4- or 6-h exposure) did not significantly alter ET secretion or ET-1 mRNA expression. In contrast, simultaneously increasing AVP(10(-8) M in the basolateral medium) and tonicity (+50 mM NaCl) for 4 h increased ET secretion (from 28.9 +/- 3.9 to 41.8 +/- 3.8 pg.h-1.mg protein-1; P = 0.029, n = 10) and ET-1 mRNA (control = 2,138 cpm/microliter, log of 3.33 +/- 0.048, n = 4; AVP + NaCl = 3,548.1 cpm/microliter, log of 3.55 +/- 0.09; P = 0.045, n = 5). Exposure of M-1 cells to hypertonic media (+50 mM NaCl or 100 mM mannitol) for 24 h was associated with a marked reduction of ET secretion (-83.9% with NaCl and -78.4% with mannitol; P < 0.0001). This reduction was attenuated, but not prevented, by the presence of AVP in the basolateral medium (-40%). ET-1 mRNA, in contrast, did not change with 24-h exposure to hypertonic media and increased when AVP was present. Results are compatible with the concept that generation of ET by collecting duct cells may contribute in a complex and time-dependent fashion to the paracrine control of collecting duct cell function.
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PMID:Synthesis and secretion of endothelin in a cortical collecting duct cell line. 877 Jan 64


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