UNIPROT:P41181 - FACTA Search

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Query: UNIPROT:P41181 (collecting duct)
5,183 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Quantitative ligand binding autoradiography and in situ hybridization were employed to analyze [125I]insulin-like growth factor-I ([125I] IGF-I) and [125I]IGF-II-binding sites in human kidney sections. Binding sites for both ligands were concentrated in the inner medulla and glomeruli, with low levels present in the tubulo-interstitial cortex. Competition with cold IGF-I, IGF-II, and insulin was used to determine nonspecific binding and differentiate binding of ligands to the IGF-I and IGF-II receptors and IGF-binding proteins (IGFBPs). Nonspecific binding was less than 20% of the total for both ligands. Insulin (10(-5) mol/L), which binds to the IGF-I receptor, but not to the IGF-II receptor or IGFBPs, displaced 39 +/- 8% of [125I]IGF-I binding in glomeruli, 60 +/- 7% in the tubulo-interstitial cortex, and 32 +/- 7% in the medulla. Insulin produced no detectable decrease in [125I]IGF-II binding in any region. IGF-I (10(-8) mol/L), which binds strongly to IGFBPs, but not appreciably to the IGF-II receptor, produced reductions of 46 +/- 9%, 35 +/- 8%, and 39 +/- 12% in [125I]IGF-II binding in glomeruli, tubulo-interstitial cortex, and medulla, respectively. In situ hybridization showed that IGFBP-1-5 mRNAs were all expressed in glomeruli. IGFBP-2 mRNA was abundant in medullary collecting duct epithelium, whereas IGFBP-3, -4, and -5 mRNAs were localized in interstitial and vascular cells throughout the kidney. IGF-I and -II receptor mRNAs were widely distributed in renal epithelium. The abundance of local IGFBP gene expression was positively correlated with insulin-nondisplaceable IGF binding in specific kidney regions. In summary, [125I]IGF-I binding appears to be partitioned largely to IGFBPs in glomeruli and largely to the IGF-I receptor in the tubulo-interstitial cortex, with binding in the medulla more evenly divided. The proportion and regional distribution of [125I]IGF-II binding to IGFBPs are similar, but the balance appears to be primarily associated with the IGF-II, rather than the IGF-I, receptor. Finally, this study shows that [125I]IGF binding autoradiography combined with in situ hybridization can be used to localize and potentially quantitative expression of IGFBPs in tissue sections.
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PMID:Partition of insulin-like growth factor (IGF)-binding sites between the IGF-I and IGF-II receptors and IGF-binding proteins in the human kidney. 750 21

Antidiuretic hormone (ADH) regulates renal water excretion by altering the permeability of the collecting duct to water. ADH-responsive epithelial cells are the major cell type lining kidney tubules in the inner medulla and papilla. ADH modulates apical membrane water permeability by the insertion and removal of vesicles containing aquaporin collecting duct water channel protein (now termed AQP-2). To identify and characterize proteins responsible for trafficking of AQP-2-containing vesicles, we utilized antibody and cDNA probes to synaptobrevin b (also termed VAMP-2, for vesicle-associated membrane protein 2), a protein that mediates synaptic vesicle exocytosis in the brain and whose structural homologs are now considered to be components of a complex responsible for intracellular vesicle fusion in all cells. We now report that rat kidney inner medulla and papilla contain abundant synaptobrevin protein. Only light endosomes, one of two types of purified papillary AQP-2-containing endosomes, possess synaptobrevin. Light endosomes fuse in vitro by means of an ATP-dependent process that is significantly inhibited when endosomes are preincubated with either anti-synaptobrevin antibody or tetanus toxin. These data define a functional role for a synaptobrevin protein in the fusion of endosomes in vitro. The presence of abundant synaptobrevin proteins in endosomes containing AQP-2 water channels, as well as insulin-sensitive glucose transporters [Cain, C. C., Trimble, W. S. & Lienhard, G. E. (1992) J. Biol. Chem. 267, 11681-11684], and in cells of Malpighian tubules responsible for urine formation in insects [Chin, A. S., Burgess, R. W., Wong, B. R., Schwartz, T. L. & Scheller, R. H. (1993) Gene 131, 175-181] suggests a specialized role for synaptobrevin in vesicle-mediated membrane transport modulated by peptide hormones.
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PMID:Rat kidney papilla contains abundant synaptobrevin protein that participates in the fusion of antidiuretic hormone-regulated water channel-containing endosomes in vitro. 753 5

1. Hyperinsulinaemia is considered to be a pathogenic factor for human and experimental hypertension. Thus, the contribution of the known insulin-stimulated tubular sodium reabsorption to this aetiological process has to be discussed. 2. Rats fed a fructose-enriched diet develop hyperinsulinaemia and hypertension, providing a model for studying the regulation of the tubular sodium handling and its possible relationship to hypertension. For this purpose, the sodium transport capacity of isolated nephron segments from control rats and from rats fed a fructose-enriched diet was investigated by measurement of ouabain-sensitive 86Rb uptake and of the hydrolytic activity of Na,K-ATPase. The number and affinity of insulin receptors were estimated from the specific [125I]insulin binding. 3. In rats fed a fructose-enriched diet, mild hypertension developed during the 14-day fructose diet. There were no differences, along the nephron, in basal 86Rb uptakes and ATPase activities between control rats and fructose-induced hypertensive rats. In control rats, insulin stimulated 86Rb uptake in the proximal convoluted tubule and cortical collecting duct, but exhibited an inhibitory action in the medullary thick ascending limb. In contrast, in fructose-induced hypertensive rats, 86Rb influx remained unresponsive to insulin concentrations ranging from 10(-11) to 10(-7) mol/l in the proximal convoluted tubule and cortical collecting duct. In the medullary thick ascending limb, the threshold of inhibition was displaced from 10(-11) mol/l up to 10(-7) mol/l. Insulin binding to the proximal convoluted tubule, medullary thick ascending limb and collecting duct were similar in control rats and in rats fed a fructose-enriched diet.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Insulin unresponsiveness of tubular monovalent cation transport during fructose-induced hypertension in rats. 773 97

To determine whether decreased renal responsiveness to atrial natriuretic peptide (ANP) in diabetes is mediated by alterations in the renal ANP receptor, ANP receptor density and affinity were measured 17-20 d after streptozotocin injection and compared with values in vehicle-treated controls and streptozotocin-treated rats made euglycemic with insulin. Plasma ANP concentration was significantly greater in hyperglycemic diabetic rats than in control or euglycemic diabetic rats. Both in glomeruli and inner medulla, ANP receptor dissociation constant did not differ among the three study groups, whereas the maximum binding capacity was decreased significantly in hyperglycemic diabetics in comparison with controls and euglycemic diabetics. Glomerular clearance receptors were also decreased significantly in hyperglycemic diabetic rats in comparison with control and euglycemic diabetic rats. To determine whether the decreased number of renal ANP receptors in diabetic rats was associated with a decreased biological response, we measured ANP-dependent cyclic GMP (cGMP) accumulation by isolated glomeruli and inner medullary collecting duct cells in vitro. cGMP accumulation was significantly less in hyperglycemic diabetic rats than in controls or euglycemic diabetic rats both in the presence or absence of the phosphodiesterase inhibitor zaprinast. cGMP phosphodiesterase activity in inner medullary collecting duct cells obtained from control and hyperglycemic diabetic rats did not differ. Thus, the decreased number of biologically active ANP receptors in the kidneys of diabetic rats is accompanied by decreased biological responsiveness in vitro and provides a potential explanation for the reduction in renal sensitivity to ANP in this condition.
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PMID:Receptors for atrial natriuretic peptide are decreased in the kidney of rats with streptozotocin-induced diabetes mellitus. 776 90

The effect of insulin on water and urea transport was examined in normal isolated rat inner medullary collecting duct (IMCD). Hydraulic conductivity (Lp, x 10(-6) cm.atm-1.s-1), diffusional water permeability (Pdw, x 10(-5) cm/s) and [14C]urea permeability (x 10(-5) cm/s) were studied at 37 degrees C and pH 7.4. Insulin (6 x 10(-8) M; 200 microU/ml) added to the bath fluid enhanced Lp from 0.40 +/- 0.10 to 1.21 +/- 1.40 (P < 0.01) and Pdw from 42.40 +/- 3.40 to 58.50 +/- 5.00 (P < 0.02) and also stimulated Lp in a dose-dependent manner. In the presence of antidiuretic hormone (ADH)-stimulated Pdw (10 microU/ml), insulin increased Pdw even more. Prostaglandin E2 (10(-5) M) added to the bath reversibly increased insulin-induced Lp. Forskolin (10(-4) M) blocked the action of insulin. Colchicine (10(-4) M) and V1-receptor antagonist (10(-4) M) inhibited the development but not the maintenance of insulin-stimulated Pdw. Vanadate (2.5 x 10(-6) M) enhanced Pdw. Polymyxin B (10(-5) M) inhibited the insulin-stimulated Pdw, whereas in a glucose-free medium insulin did not enhance Pdw. Urea transport was not affected by insulin. These data suggest that insulin may enhance water transport, probably by stimulating glucose transporters, which would serve as a water channel. We cannot rule out the possibility that insulin may be eliciting existing ADH-like mechanisms of water transport, beyond the microtubule step, to establish water transport.
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PMID:Effect of insulin on water and urea transport in the inner medullary collecting duct. 816 Jul 87

To investigate the differentiation of the ampullary collecting duct cells into adult principal and intercalated cells, the embryonic cortex of newborn New Zealand rabbit kidney was isolated and brought in culture. With this culture technique the ampullary cells formed a polarized collecting duct epithelium which was kept under permanent exchange of medium and in the presence of aldosterone, arginine vasopressin and/or insulin. After 14 days of perfusion culture the epithelia showed light and dark cells resembling the principal and intercalated cells of the adult collecting duct. The differentiation from embryonic into adult collecting duct cells was controlled by applying the monoclonal antibody CD 7. Independent of the hormonal treatment all of the epithelial cells matured in culture and expressed the CD 7 antigen. This corresponded with the situation found within the adult kidney, where the CD 7 antigen was localized in all principal and intercalated (IC) cells, whereas the embryonic ampullary epithelium in the neonatal kidney remained negative. A differentiation feature of the beta-type intercalated cell was investigated by labeling the cultured epithelia with peanut agglutinin (PNA). In contrast to the CD 7 antigen the development of PNA binding was highly dependent of time and individual hormone administration. While in control epithelia only 8% of PNA positive cells were found, aldosterone induced epithelia revealed 72% PNA labeled cells. The combination of aldosterone and insulin increased the number of PNA-positive cells to 90%. By scanning electron microscopy it could further be shown that several isoforms of cells were reactive with PNA. Thus, in culture the PNA label is not restricted to the typical beta-type IC cells.
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PMID:Aldosterone modulates PNA binding cell isoforms within renal collecting duct epithelium. 823 Oct 25

Small-conductance, ATP-sensitive K(+)-channels (KATP) localized in apical membranes of both thick ascending limb of the loop of Henle and cortical collecting duct cells may be involved in Na+ reabsorption and K+ secretion in the mammalian kidney. Possible pharmacologic tools to evaluate such an hypothesis may be the antidiabetic sulfonylureas which block K(+)-channels in pancreatic beta-cells. In saline-loaded conscious rats, glyburide (GLY) dose-dependently increased urinary Na+ excretion with little change in urinary K+ excretion after i.p. administration (10-100 mg/kg). In renal clearance studies, GLY at 25 mg/kg i.v. increased Na+ excretion 350% during the first hour post-treatment without affecting K+ excretion, glomerular filtration rate, mean arterial pressure or heart rate. GLY at 50 mg/kg was no more natriuretic than the 25 mg/kg dose, whereas 12.5 mg/kg of GLY increased Na+ excretion 200%. The change in Na+ excretion produced by 25 mg/kg of GLY in streptozotocin-induced diabetic rats was significantly greater than the change after drug vehicle in these animals. It is unlikely that the natriuresis produced by GLY is secondary to changes in plasma insulin and/or glucose because the doses used were far above GLY's insulin-releasing action (i.e., all natriuretic doses would have produced maximal insulin release) and GLY was natriuretic in streptozotocin-induced diabetic rats. It is possible that GLY interferes with reabsorption of Na+ by blocking KATP and thereby interrupting K+ recycling and Na(+)-2Cl(-)-K+ cotransport in the loop of Henle.
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PMID:Unique natriuretic properties of the ATP-sensitive K(+)-channel blocker glyburide in conscious rats. 849 33

1. The collecting duct is involved in the whole antinatriuretic effect of insulin, as indicated in vitro by the stimulatory effect of the hormone on ouabain-sensitive 86Rb+ uptake. Since Na+,K(+)-ATPase drives Na+ reabsorption, the contribution of the Na+ pump to the effect of insulin was investigated in rat isolated cortical and outer medullary collecting duct. 2. Insulin enhanced ouabain-sensitive 86Rb+ uptake in the absence, as well as in the presence, of either 5 x 10(-4) M amiloride or 10(-3) M hydrochlorothiazide (HCT). Maximal ouabain-sensitive 86Rb+ uptake, measured in Na(+)-loaded tubules, was also enhanced by insulin. The insulin effect persisted both in the absence of external Na+, when the Na+,K(+)-ATPase operates in a Rb(+)-Rb+ exchange mode, and in tubules depolarized by a high external concentration (20 mM) of Rb+ or by addition of 3 mM Ba2+. 3. Insulin treatment did not alter the intracellular Na and K concentrations, the specific binding of [3H]ouabain measured in intact tubules, or the hydrolytic activity of Na+,K(+)-ATPase measured after permeabilization of the tubule cells. 4. In conclusion, in the rat collecting duct, insulin increased Na+,K(+)-ATPase-mediated cation transport independently of Na+ availability, membrane potential and recruitment of pump units. The effect of insulin was lost after cell permeabilization, suggesting the presence of a cytosolic factor which controls the turnover of Na+,K(+)-ATPase.
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PMID:Effect of insulin on Na+,K(+)-ATPase in rat collecting duct. 856 53

Expression of human keratinocyte growth factor (KGF/FGF-7) was directed to hepatocytes during the later period of mouse gestation using a human apolipoprotein E (ApoE) gene promoter and its associated liver-specific enhancer. Human KGF was detectable in liver extracts and serum prepared from e17.5-e19.5 embryos, concomitant with the appearance of morphological abnormalities in several organs which express KGF receptor. The most striking phenotypic aberration in the ApoE-hKGF transgenic embryos was marked hyperplasia and cystic dilation of the cortical and medullary kidney collecting duct system, a phenotype resembling infantile polycystic kidney disease in humans. Transgenic embryos had enlarged livers, with prominent biliary epithelial hyperplasia, and also exhibited enhanced bronchiolar epithelial and type II pneumocyte proliferation. There was variable hyperplasia of intestinal epithelia, and urothelium of the urinary bladder and ureters. When compared to age-matched littermate controls, marked epidermal papillomatous acanthosis and hyperkeratosis in the skin, with a notable decrease in the number of developing hair follicles was seen in transgenic embryos. The pancreas exhibited significant ductal hyperplasia, with an increase in the number of ductal epithelial cells staining positive for insulin expression. High systemic levels of KGF during the latter stages of embryogenesis causes abnormalities in epithelial growth and differentiation within multiple organ systems and results in perinatal lethality. Correct temporal and spatial expression of KGF during the latter stages of organ development is likely to play a critical role in mesenchymal-epithelial signaling required for normal embryonic growth and development.
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PMID:Expression of keratinocyte growth factor in embryonic liver of transgenic mice causes changes in epithelial growth and differentiation resulting in polycystic kidneys and other organ malformations. 866 36

Hereditary diabetes insipidus can occur in two forms: the first, referred to as central diabetes insipidus, is responsive to vasopressin whereas the second, termed nephrogenic diabetes insipidus, is resistant to treatment. Recent advances in molecular genetics have contributed to elucidate the pathogenesis of these affections. Familial central diabetes insipidus depicts two unsimilar illnesses. The first, characterized by an autosomal dominant transmission, is of delayed onset and worsens progressively all through life. It is related to a heterozygous mutation of the vasopressin precursor gene mainly involving either the sequence encoding for the signal peptide or the one encoding for neurophysin II, the hormone carrier protein. Mutations described to date are responsible for impairment of vasopressin precursor transportation and processing. Therefore mutant protein accumulates in the posterior pituitary which is involved in the persistant bright spot seen on magnetic resonance imaging. The second illness or Wolfram syndrome, autosomal recessive, associates obligatory features: insulin-dependant diabetes, bilateral optic atrophy and more inconstantly: diabetes insipidus, deafness, genito-urinary and neuropsychiatric disturbances. The cause of this syndrome, still unknown, may involve mitochondrial ADN mutations. Familial nephrogenic diabetes insipidus, of neonatal onset, are mainly X-linked and associated to mutations in the V2 receptor gene. About 60 mutations have been described until now. Some rare cases, transmission of which is autosomal recessive, result from homozygous mutations of aquaporin 2 gene, a water channel involved in the water reabsorption in the renal collecting duct. Other mutations will be probably discovered in future. In conclusion, familial diabetes insipidus constitutes an interesting pathogenic model because it may be explained by impairment of vasopressin gene precursor as well as by abnormalities of renal receptor or post receptor mechanisms of the hormone.
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PMID:[Congenital diabetes insipidus. Recent advances in molecular genetics]. 868 70

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