Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01185 (vasopressin)
 23,126 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Freshly isolated rabbit proximal tubules (PT), confluent primary rabbit proximal tubule cultures (PTC) and LLC-PK1 cells were characterised. Brushborder enzyme activities were lower in PTC than in LLC-PK1: ratios were 0.026 for alkaline phosphatase (AP), 0.458 for alanine aminopeptidase (AAP) and 0.514 for gamma-glutamyl transpeptidase (GGT). PT/PTC ratios were 79.7 for AP, 7.96 for AAP and 3.45 for GGT. Specific activities of hexokinase (HK) and lactate dehydrogenase (LDH) were high in cultured cells as compared to PT: PT/PTC ratios were 0.063 and 0.033, while PTC/LLC-PK1 ratios were 0.406 and 1.19 for HK and LDH respectively. PTC/LLC-PK1 ratios were 2.21 for Na/K ATPase, 2.07 for succinate dehydrogenase, 1.12 for cathepsin B, 0.607 for N-acetyl-beta-D-glucosaminidase and 8.98 for glutathione-S-transferase. Adenylate cyclase response to parathormone (PTH), was similar in PTC and PT, but stimulated/basal ratios were higher in PT than in PTC. LLC-PK1 cells were stimulated by thyrocalcitonin (SCT), arginin-vasopressin (AVP) and PTH; stimulated/basal ratios ranked AVP greater than PTH greater than SCT. Differences between both types of cultures affect the choice of in vitro model for nephrotoxicity studies.
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PMID:Adenylate cyclase responses and biochemical characterization of primary rabbit proximal tubular cell cultures and LLC-PK1 cells. 228 70

Fractional excretion of lithium (FELi+) has been proposed as an index of fluid delivery to the distal nephron. The increase in FELi+ after the "loop diuretic" furosemide indicates that this postulate may not be valid unless furosemide acts in the proximal tubules. We studied the effect of furosemide (40 mg iv as bolus, followed by 20 mg/h infusion for 90 min) in eight healthy male subjects during maximal water diuresis. Special care was taken to exactly replace urinary losses. Furosemide greatly increased fractional excretion of sodium, from 1.3 +/- 0.4 to 27.8 +/- 3.9%, and water, from 14.2 +/- 1.7 to 38.2 +/- 3.7% (P less than 0.01). There was a disproportionately large increase in FELi+ from 30.3 +/- 3.0 to 53.7 +/- 2.9% (P less than 0.01), whereas fractional excretion of some other alleged proximal markers increased to a lesser extent. Lysine vasopressin, infused at the end of the experiment (n = 7), caused only a small increase in urine osmolality from 225 +/- 17 to 241 +/- 17 mosmol/kg (P less than 0.01), indicating that medullary hyperosmolality had been largely abolished. The most likely explanation of these results is that furosemide has a moderate action in the proximal tubules, and at the same time inhibits preexistent lithium absorption in Henle's loop. In addition, the large difference between FELi+ and maximal urine flow remaining after furosemide suggests that, despite the decreased medullary osmotic gradient, water backdiffusion is unaltered by furosemide or that lithium concentration in the proximal tubule is changed by furosemide.
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PMID:Does lithium clearance reflect distal delivery in humans? Analysis with furosemide infusion. 233 Sep 75

The existence and identity of protein water transporters in biological membranes has been uncertain. Osmotic water permeability (Pf) was measured in defolliculated Xenopus oocytes microinjected with water or mRNA from kidney cortex, kidney papilla, reticulocyte, brain, and muscle. Pf was measured by quantitative image analysis from the time course of oocyte swelling in response to an osmotic gradient. When assayed at 10 degrees C, Pf in water-injected oocytes increased from (3.6 +/- 0.9) x 10(-4) cm/s (S.D., n = 16) to 74 x 10(-4) cm/s with addition of amphotericin B, showing absence of unstirred layers. At 48-72 h after injection of 50 ng of unfractionated mRNA, Pf (in cm/s x 10(-4] was: 4.0 +/- 1.5 (rabbit brain, n = 15), 4.2 +/- 1.8 (rabbit muscle, n = 10), 18.4 +/- 6.3 (rabbit reticulocyte, n = 20), 16.1 +/- 5.6 (rat renal papilla, n = 24), 12.9 +/- 6.3 (rat renal cortex, n = 20), 14.4 +/- 6.1 (rabbit renal papilla, n = 15), and 11.8 +/- 3.4 (rabbit renal cortex, n = 8). In oocytes injected with mRNA from rat renal papilla, Pf was inhibited reversibly by 0.3 mM HgCl2 (4.1 +/- 1.6, n = 10); expressed water channels from kidney and red cell had activation energies of less than 4 kcal/mol. These results show functional oocyte expression of water channels from red cell, kidney proximal tubule (cortex), and the vasopressin-sensitive kidney collecting tubule (papilla), indicating that water channels are proteins, and providing an approach for the expression cloning of water channels.
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PMID:Expression of mRNA coding for kidney and red cell water channels in Xenopus oocytes. 239 28

Postsynaptic binding sites for alpha 1 and alpha 2 adrenoceptor ligands are found in abundance in the renal cortex of several species, with reports of 2-3 times as many alpha 2 as alpha 1 sites. These alpha adrenoceptor subtypes can potentially influence salt and water excretion through both vascular and tubular effects. Renal vascular resistance in dogs is increased by both alpha adrenoceptor subtype agonists but alpha 1 agonists are more potent. In rats, alpha 2, agonists have almost no effect on the renal circulation whereas alpha 1 agonists are capable of intense renal vasoconstriction. The mechanisms by which alpha 2 agonists increase glomerular filtration rate are not yet clear and may involve the secondary release of hormones affecting glomerular dynamics and permeability. Thus, an abundance of alpha 2 adrenoceptor binding sites in whole cortical homogenate of rat kidneys with little demonstrable vascular effect of alpha 2 agonist suggests that the preponderance of these receptors lies instead on the tubular epithelium. Alpha-1 adrenoceptors are probably responsible for the increased Na reabsorption from the proximal tubule and the anti-natriuresis following low level renal nerve stimulation. In contrast, an alpha 2 agonist such as guanabenz produces a diuresis by reducing the release of vasopressin and by antagonizing its hydrosmotic effect on the nephron, and a modest natriuresis by decreasing medullary interstitial osmolality and reducing passive Na reabsorption.
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PMID:Role of alpha-2 receptors in the regulation of renal function. 241 45

Microvillar membranes derived from the brush border of the renal proximal tubule are very rich in peptidases. Pig kidney microvilli contain endopeptidase-24.11 associated with a battery of exopeptidases. The manner by which some neuropeptides are degraded by the combined attack of the peptidases of this membrane has been investigated. The contribution of individual peptidases was assessed by including inhibitors (phosphoramidon, captopril, amastatin and di-isopropyl fluorophosphate) with the membrane fraction when incubated with the peptides. Substance P, bradykinin and angiotensins I, II and III and insulin B-chain were rapidly hydrolysed by kidney microvilli. Oxytocin was hydrolysed much more slowly, but no products were detected from [Arg8]vasopressin or insulin under the conditions used for other peptides. The peptide bonds hydrolysed were identified and the contributions of the different peptidases were quantified. For each of the susceptible peptides, the main contribution came from endopeptidase-24.11 (inhibited by phosphoramidon). Peptidyl dipeptidase A (angiotensin-I-converting enzyme) was of less importance, even in respect of angiotensin I and bradykinin. When [2,3-Pro3,4-3H]bradykinin was also investigated at a lower concentration (20 nM), the conclusions in regard to the contributions of the two peptidases were unchanged. The possibility that endopeptidase-24.11 might attack within the six-residue disulphide-bridged rings of oxytocin and vasopressin was examined by dansyl(5-dimethylaminonaphthalene-1-sulphonyl)ation and by reduction and carboxymethylation of the products after incubation. Additional peptides were only observed after prolonged incubation, consistent with hydrolysis at the Tyr2-Ile3 and Tyr2-Phe3 bonds respectively. These results show that a range of neuropeptides are efficiently degraded by microvillar membranes and that endopeptidase-24.11 plays a key role in this process.
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PMID:Metabolism of neuropeptides. Hydrolysis of the angiotensins, bradykinin, substance P and oxytocin by pig kidney microvillar membranes. 243 10

Pos and Pd, osmotic and diffusive water permeability coefficients of isolated rabbit proximal tubule (PT) cells (expressed per cm2 of real cell membrane area, in microns/sec) are: Pos 396; Pd, 22; Pos/Pd, 18 (control), and after exposure to parachloromercuribenzenesulfonate (pCMBS): Pos, 32; Pd, 10; Pos/Pd, 3. The sulfhydryl reagent dithiothreitol (DTT) reverts pCMBS action. The activation energies (kcal/mol) are Pos, 3.2 (control); 9.2 (pCMBS); Pd, 5.2 (control) and 9.1 (pCMBS). Thus water channels pierce the control plasma membrane and are reversibly closed by pCMBS. High control PT permeabilities are comparable with those of amphibian urinary bladder and collecting tubules (CT) stimulated with antidiuretic hormone (ADH), and low PT (pCMBS) values with those of CT in the resting state, respectively. Transcellular permeability is regulated in PT by the state of sulfhydryl groups and in CT by ADH induced insertion (or, no ADH, suppression) of water channels. In PT (a) large extracellular markers are dragged by water flow indicating extracellular solute-water interaction, (b) transepithelial Pos is much higher than transcellular Pos. Therefore water also flows paracellularly, in addition to the transcellular flow. In PT paracellular permeability is increased if urea in lumen is higher than in blood. It is reduced in the reverse situation. In CT paracellular permeability is virtually zero (resting condition). It may be increased by high lumen urea. Thus, paracellular permeability (which is significant in control PT and zero in CT) can be regulated by changes in the transepithelial urea concentrations. Transcellular permeability depends on the number of channels/cm2 epithelium, their probability of being opened and their individual permeability.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Channels for water flow in epithelia: characteristics and regulation. 248

The case of a 7-year-old boy with the normotensive form of "chloride-shunt" syndrome is described. An unusual feature was the clinical presentation with lithiasis, caused by marked hypercalciuria of renal origin. The present studies were carried out to investigate the nature of the renal tubular defect. Indices for proximal and distal sodium chloride reabsorption were increased during hypotonic saline diuresis. Baseline sodium chloride excretion was low but increased above the range of control values after acute furosemide administration. Baseline potassium excretion was low, was not modified by the infusion of sodium chloride and increased significantly during infusions of sodium sulphate or sodium bicarbonate. Calcium excretion remained unchanged during sodium chloride, sodium sulphate or sodium bicarbonate infusions, but increased after furosemide administration. Nasal insufflation of 1-desamino-8-D-arginine-vasopressin induced both an increase in potassium excretion and a decrease in calcium and magnesium excretion. Plasma atrial natriuretic peptide was increased and was not significantly modified by infusion of hypertonic saline or acute administration of furosemide. These findings indicate that the primary renal abnormality appears to be an enhanced tubular reabsorption of sodium chloride, apparently present in the proximal tubule and the ascending loop of Henle. The associated presence of hypercalciuria also suggests a transport defect in the distal tubule. Decreased potassium excretion probably depends on a voltage-shunting defect in the cortical collecting tubule, which can be reversed by increasing the delivery of non-reabsorbable anions or by enhancing the conductance of the luminal membrane.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:"Chloride-shunt" syndrome: an overlooked cause of renal hypercalciuria. 253 69

Cultured human renal cortical epithelial cells (NHK-C) were examined for functional and morphologic characteristics of the proximal tubule. Cultures were established by using cells isolated by progressive enzymatic dissociation from the extreme outer cortex of the normal human kidney. Cells were subcultured and used at passages 3 through 8. Cell uptake of alpha-methyl-D-glucoside (AMG), inorganic phosphate (Pi) and L-alanine was found to be dependent on the presence of Na+ in the incubation medium, and uptake increased with incubation time up to 30 minutes. Na+-dependent AMG uptake was inhibited 67% by phlorizin (1 mmol/L), and Pi uptake was inhibited 89% by parathyroid hormone (PTH) (10(-6) mol/L). Intracellular cyclic adenosine monophosphate was increased 28-fold after exposure to 10(-6) mol/L PTH but was increased only 2-fold by the same concentration of vasopressin. The cells exhibited endocytotic activity and possessed maltase, leucine aminopeptidase, and gamma-glutamyltranspeptidase, enzymes located exclusively in the brush border membranes of proximal tubule cells. NHK-C cultures were structurally heterogeneous, made up of a mixed-cell population with predominant epithelial-like morphology. Epithelial cells had cuboidal form, solitary cilia, and short, irregularly distributed apical microvilli. These cultures also formed multicellular hemicysts, but only through passage 3. NHK-C cultures showed a dramatic attenuation of proliferative activity at passages 8 through 10. These data show that subcultured cells derived from the outer cortex of the normal human kidney retain a number of functional characteristics typical of the proximal tubule.
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PMID:Proximal tubule characteristics of cultured human renal cortex epithelium. 253 26

Proximal tubules were prepared from rat kidney cortex by collagenase digestion and purified by Percoll gradient centrifugation. Their enrichment was estimated by comparing the specific activities of various cell-specific enzymes in homogenates of renal cortex and of the isolated tubules. The tubules were cultured in a 50:50 mixture of Dulbecco's modified Eagle's and Ham's F12 media supplemented with insulin, transferrin, epidermal growth factor, hydrocortisone, and prostaglandin E1. After 2 to 3 d an extensive outgrowth of epithelial cells developed from the attached tubules. After 5 to 7 d near confluent monolayers were obtained. Hormonal responsiveness, marker enzyme activities, and transport properties were determined to further characterize the primary cultures. The cultured cells exhibited increased cyclic AMP production in response to parathyroid hormone but not calcitonin or vasopressin, consistent with the absence of cells derived from distal and collecting tubules. The cells also retained significant levels of 25-hydroxyvitamin D3-1 alpha-hydroxylase, alkaline phosphatase, and gamma-glytamyl-transpeptidase, three enzymes that are primarily associated with the proximal tubule. The cultured epithelial cells also exhibit a Na+-dependent phosphate and glucose transport systems. Therefore, the cells retain many functional properties that are characteristic of proximal tubules. Thus, the primary cultures should be suitable for the study of processes that occur specifically within this segment of the rat nephron.
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PMID:Characterization of primary cell cultures derived from rat renal proximal tubules. 254 89

A culture system is described in which rat kidney proximal tubule epithelial cells (RPTE) can be prepared with good yield and high viability and grown in culture under serum-free conditions. The cells require EGF, insulin, cholera toxin and either 1% dialyzed serum or a complex of bovine serum albumin with oleic acid (BSA/OA). The cells can be maintained for long periods of time and express several markers for RPTE. The cells have both alkaline phosphatase and gamma-glutamyltransferase activity and respond to parathyroid hormone but not vasopressin. The specific activity of gamma-glutamyltransferase decreases when the cells begin to grow, but increases when they reach confluence. Extracellular calcium plays a role in the induction of gamma-glutamyltransferase in confluent cells. Cells grown in media containing low calcium, i.e. less than 0.4 mM, have reduced specific activity of gamma-glutamyltransferase. Extracellular calcium also alters the morphology of the cells in that cells grown in low calcium are single cells or loose clusters suggesting poor cell-cell contact. When the calcium is raised to 1.0 mM, the cells change their shape and organization to adopt the morphology of cells maintained continuously in 1.0 mM calcium. The cells can be passaged onto plastic surfaces which have been coated with collagen but cannot be subcultured on uncoated or serum coated plastic. This culture system will be a useful model for the investigation of renal carcinogenesis and the role of cell proliferation in that process.
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PMID:Rat kidney proximal tubule cells in defined medium: the roles of cholera toxin, extracellular calcium and serum in cell growth and expression of gamma-glutamyltransferase. 256 95


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