Organic solutes in fluid absorption by renal proximal convoluted tubules

1976 ◽  
Vol 231 (2) ◽  
pp. 627-637 ◽  
Author(s):  
M Burg ◽  
C Patlak ◽  
N Green ◽  
D Villey
Keyword(s):  
Epithelial Cell ◽  
Organic Solutes ◽  
Fluid Absorption ◽  
Transepithelial Voltage ◽  
Convoluted Tubules ◽  
Proximal Convoluted Tubules

Proximal convoluted tubules were dissected from rabbit kidneys and perfused with artificial solutions in vitro. The effect of various organic solutes on rate of fluid absorption and transepithelial voltage was tested by removing solutes from or adding them to perfusate and/or bath. Omission of albumin from the bath caused rate of fluid absorption to descrease 33% without any change in voltage. Omission of glucose, lactate, alanine, and citrate from the bath had no effect. In contrast, when they were removed from perfusate, rate of fluid absorption fell by 45-75% (depending on whether they were replaced by NaCl or mannitol and NaCl), and voltage (normally negative in lymen) decreased to near zero. Adding glucose or alanine individually to perfusate caused a small increase in rate of fluid absorption and a relatively large increase in voltage. alpha-Methyl-D-glucoside and cycloleucine (which are transported but not metabolized) had effects similar to glucose and alanine, except that voltage changes were not as great. Phlorizin (10(-5) M in perfusate) had the same effect as removing glucose from perfusate. When glucose and alanine were added to perfusate, epithelial cell swelled significantly. Lactate and citrate also caused rate of fluid absorption to increase when they were added to perfusate, but they did not affect transepithelial voltage nor did they cause cells to swell significantly. Possible mechanisms of these effects and the role of organic solutes in fluid absorption by proximal convoluted tubules are discussed.

Bicarbonate transport by isolated perfused rabbit proximal convoluted tubules

1977 ◽  
Vol 233 (4) ◽  
pp. F307-F314 ◽  
Author(s):  
M. Burg ◽  
N. Green
Keyword(s):  
Hydrogen Ion ◽  
Bicarbonate Transport ◽  
Fluid Absorption ◽  
The Mean ◽  
Tubule Cells ◽  
The Relationship ◽  
Convoluted Tubules ◽  
Mean Concentration ◽  
Proximal Convoluted Tubules

Proximal convoluted tubules were dissected from rabbit kidneys and perfused in vitro in order to investigate the relationship between the reabsorption of fluid and of bicarbonate. Bicarbonate was absorbed when it was initially present in the perfusate. At slow rates of perfusion the mean concentration of total CO2 was 9 mM in collected fluid with 25 mM bicarbonate in the bath. At faster rates of perfusion the mean rate of reabsorption was 13.6 pmol cm-1 tubule length s-1. Absorption of bicarbonate was inhibited to a large but not complete extent by elimination of sodium from the perfusate and bath or potassium from the bath, and by addition of ouabain. It was not inhibited by elimination of the organic solutes from the perfusate nor by elimination of chloride from the perfusate and bath. Considered with previous measurements of fluid absorption these results are consistent with the existence of a linked sodium-for-hydrogen ion exchange mechanism at the luminal border of the tubule cells, but there are other possibilities which are discussed. Additionally, the effect of acetazolamide was investigated. The drug virtually completely inhibited bicarbonate absorption and inhibited fluid absorption by 30-40%.

Determination of chloride and bicarbonate permeabilities in proximal convoluted tubules

1981 ◽  
Vol 241 (4) ◽  
pp. F386-F394 ◽  
Author(s):  
C. Holmberg ◽  
J. P. Kokko ◽  
H. R. Jacobson
Keyword(s):  
Proximal Tubules ◽  
Rabbit Serum ◽  
Exchange Diffusion ◽  
Permeability Coefficients ◽  
Transepithelial Voltage ◽  
Convoluted Tubules ◽  
Co2 Addition ◽  
Proximal Convoluted Tubules

In late proximal tubules volume reabsorption linked to passive ion flows relies on the existence of differing permeability coefficients to Cl- and HCO3(-) (PCl greater than PHCO3). We measured these permeability coefficients in late segments of rabbit superficial (SFPCT) and juxtamedullary (JMPCT) proximal convoluted tubules perfused in vitro. PHCO3 and P36Cl were determined in tubules bathed in rabbit serum and perfused with a serum ultrafiltrated titrated with H2SO4 to [HCO3(-)] of 4 mM. Active transport, transepithelial voltage, and HCO3(-) reabsorption were inhibited by cooling (21 degrees C) and 10(-4) M acetazolamide. P36Cl and PHCO3 were calculated from 36Cl disappearance from and total CO2 addition to the perfusate. P36Cl in SFPCT was twice that in JMPCT but PHCO3 was the same in both segments. P36Cl exceeded PHCO3 only in SFPCT. To exclude exchange diffusion from contributing to P36Cl, additional tubules were perfused with ultrafiltrate titrated with HCl.P36Cl and simultaneously measured PCl (lumen-to-bath net chemical Cl- flux) were identical. We conclude: 1) SFPCT and JMPCT are heterogeneous with respect to Cl- permeability; 2) relative Cl--to-HCO3(-) permeabilities predict that anion gradients present in late portions of proximal tubules would support more volume reabsorption linked to passive ion flows in SF than in JMPCT; 3) no significant Cl- exchange diffusion exists in proximal tubules.

PTH inhibition of bicarbonate transport by proximal convoluted tubules

1980 ◽  
Vol 239 (2) ◽  
pp. F127-F134 ◽  
Author(s):  
T. D. McKinney ◽  
P. Myers
Keyword(s):  
Parathyroid Hormone ◽  
Cyclic Amp ◽  
Co2 Concentration ◽  
Bicarbonate Transport ◽  
Co2 Absorption ◽  
Fluid Absorption ◽  
Dibutyryl Cyclic Amp ◽  
Convoluted Tubules ◽  
Proximal Convoluted Tubules

These studies examined the effect of parathyroid hormone (PTH), dibutyryl cyclic AMP DBcAMP, and 8-bromo-cyclic AMP BrcAMP on HCO3- transport by rabbit superficial proximal convoluted tubules perfused in vitro. Bicarbonate was estimated as total CO2 measured microcalorimetrically. At slow perfusion rates with 25 mM HCO3- in the perfusate and bath, PTH (0.1 U/ml in the bath) caused the total CO2 in tubular fluid to rise from 10.2 to 19.9 mM. The hormone had no effect on the total CO2 concentration in tubules perfused with HCO3(-)-free perfusates. With HCO3(-) in the perfusate and bath, PTH reduced the rates of fluid and total CO2 absorption to 57 and 48% of control values, respectively. PTH had no effect on the rates of fluid absorption and total CO2 secretion when HCO3(-)-free perfusates were used. The effects of DBcAMP and BrcAMP (10(-7) M in the bath) were similar to those of PTH. 5'-AMP (10(-6) M in the bath) did not alter the total CO2 concentration of tubular fluid when the tubules were perfused at slow rates with HCO3- in the perfusate and bath. Ouabain (10(-5) M in the bath) caused the total CO2 concentration in tubules perfused at slow rates with HCO3--free perfusates to rise from 8.9 to 12.7 mM. PTH caused no further change in the total CO2 concentration in the presence of ouabain.

scholarly journals Neuropeptide Y (NPY) promotes inflammation-induced tumorigenesis by enhancing epithelial cell proliferation

2017 ◽  
Vol 312 (2) ◽  
pp. G103-G111 ◽  
Author(s):  
Sabrina Jeppsson ◽  
Shanthi Srinivasan ◽  
Bindu Chandrasekharan
Keyword(s):  
Cell Proliferation ◽  
Epithelial Cell ◽  
Neuropeptide Y ◽  
Intestinal Inflammation ◽  
Enteric Neurons ◽  
Intestinal Epithelial ◽  
Epithelial Proliferation ◽  
Proliferation And Apoptosis

We have demonstrated that neuropeptide Y (NPY), abundantly produced by enteric neurons, is an important regulator of intestinal inflammation. However, the role of NPY in the progression of chronic inflammation to tumorigenesis is unknown. We investigated whether NPY could modulate epithelial cell proliferation and apoptosis, and thus regulate tumorigenesis. Repeated cycles of dextran sodium sulfate (DSS) were used to model inflammation-induced tumorigenesis in wild-type (WT) and NPY knockout ( NPY−/−) mice. Intestinal epithelial cell lines (T84) were used to assess the effects of NPY (0.1 µM) on epithelial proliferation and apoptosis in vitro. DSS-WT mice exhibited enhanced intestinal inflammation, polyp size, and polyp number (7.5 ± 0.8) compared with DSS- NPY−/− mice (4 ± 0.5, P < 0.01). Accordingly, DSS-WT mice also showed increased colonic epithelial proliferation (PCNA, Ki67) and reduced apoptosis (TUNEL) compared with DSS- NPY−/− mice. The apoptosis regulating microRNA, miR-375, was significantly downregulated in the colon of DSS-WT (2-fold, P < 0.01) compared with DSS- NPY−/−-mice. In vitro studies indicated that NPY promotes cell proliferation (increase in PCNA and β-catenin, P < 0.05) via phosphatidyl-inositol-3-kinase (PI3-K)-β-catenin signaling, suppressed miR-375 expression, and reduced apoptosis (increase in phospho-Bad). NPY-treated cells also displayed increased c-Myc and cyclin D1, and reduction in p21 ( P < 0.05). Addition of miR-375 inhibitor to cells already treated with NPY did not further enhance the effects induced by NPY alone. Our findings demonstrate a novel regulation of inflammation-induced tumorigenesis by NPY-epithelial cross talk as mediated by activation of PI3-K signaling and downregulation of miR-375. NEW & NOTEWORTHY Our work exemplifies a novel role of neuropeptide Y (NPY) in regulating inflammation-induced tumorigenesis via two modalities: first by enhanced proliferation (PI3-K/pAkt), and second by downregulation of microRNA-375 (miR-375)-dependent apoptosis in intestinal epithelial cells. Our data establish the existence of a microRNA-mediated cross talk between enteric neurons producing NPY and intestinal epithelial cells, and the potential of neuropeptide-regulated miRNAs as potential therapeutic molecules for the management of inflammation-associated tumors in the gut.

scholarly journals toxB Gene on pO157 of Enterohemorrhagic EscherichiacoliO157:H7 Is Required for Full Epithelial Cell Adherence Phenotype

2001 ◽  
Vol 69 (11) ◽  
pp. 6660-6669 ◽  
Author(s):  
Ichiro Tatsuno ◽  
Masanori Horie ◽  
Hiroyuki Abe ◽  
Takeyoshi Miki ◽  
Kozo Makino ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Bacterial Infection ◽  
Intestinal Epithelium ◽  
Secreted Proteins ◽  
Cell Adherence ◽  
Full Adherence ◽  
Infection Study ◽  
Phenotype Expression

ABSTRACT Adherence of enterohemorrhagic Escherichia coli (EHEC) to the intestinal epithelium is critical for initiation of a bacterial infection. An in vitro infection study previously indicated that EHEC bacteria initially adhere diffusely and then proliferate to develop MC, a process that is mediated by various secreted proteins, such as EspA, EspB, EspD, Tir, and intimin, as well as other putative adherence factors. In the present study, we investigated the role of a large 93-kb plasmid (pO157) in the adherence of O157:H7 (O157Sakai) and found the toxB gene to be involved in the full adherence phenotype. A pO157-cured strain of O157Sakai (O157Cu) developed microcolonies on Caco-2 cells; however, the number of microcolonies was lower than that of O157Sakai, as were the production and secretion levels of EspA, EspB, and Tir. Introduction of a mini-pO157 plasmid (pIC37) composed of thetoxB and ori regions restored full adherence capacity to O157Cu, including production and secretion of the proteins. In contrast, introduction of a pO157 mutant possessingtoxB::Km into O157Cu could not restore the full adherence phenotype. Expression of truncated versions of His-tagged ToxB also promoted EspB production and/or secretion by O157Cu. These results suggest that ToxB contributes to the adherence of EHEC to epithelial cells through promotion of the production and/or secretion of type III secreted proteins.

scholarly journals Absorption of Hemoglobin Iron: The Role of Xanthine Oxidase in the Intestinal Heme-Splitting Reaction

Blood ◽  
1970 ◽  
Vol 35 (1) ◽  
pp. 94-103 ◽  
Author(s):  
R. BEN DAWSON ◽  
SHEILA RAFAL ◽  
LEWIS R. WEINTRAUB
Keyword(s):  
Epithelial Cell ◽  
Xanthine Oxidase ◽  
Intestinal Epithelial Cell ◽  
Oxidase Inhibitor ◽  
Small Intestinal Mucosa ◽  
Intestinal Epithelial ◽  
Sephadex Column ◽  
Xanthine Oxidase Inhibitor

Abstract Heme from ingested hemoglobin—59Fe is taken into the epithelial cell of the small intestinal mucosa of the dog and the 59Fe subsequently appears in the plasma bound to transferrin. A substance was demonstrated in homogenates of the mucosa which releases iron from a hemoglobin substrate in vitro. Thus: (1) The addition of catalase to the mucosal homogenate reduces the "heme-splitting" reaction. In contrast, sodium azide, a catalase inhibitor, potentiates the reaction. This suggests that a peroxide generating system participates in the "heme-splitting" reaction. (2) Xanthine oxidase, an enzyme present in the intestinal epithelial cell, produces H2O2 by oxidation of its substrate. The addition of allopurinol, a xanthine oxidase inhibitor, to the intestinal mucosal homogenate diminishes the "heme-splitting" reaction. (3) Fractionation of the 50,000 Gm. supernatant of the mucosal homogenate on a G-200 Sephadex column shows the "heme-splitting" activity to have the same elution volume as xanthine oxidase, indicating a similar molecular weight. (4) The addition of a mucosal homogenate to a xanthine substrate results in the production of uric acid. These data suggest that xanthine oxidase in the intestinal epithelial cell is important in the release of iron from absorbed heme. The enzyme mediates the "heme-splitting" reaction by the generation of peroxides which, in turn, oxidize the alpha-methene bridge of the heme ring releasing iron and forming biliverdin.

Possible role of calcium in parathyroid hormone actions in rabbit renal proximal tubules

1986 ◽  
Vol 250 (5) ◽  
pp. F942-F948
Author(s):  
N. Yanagawa ◽  
O. D. Jo
Keyword(s):  
Parathyroid Hormone ◽  
Proximal Tubules ◽  
Inhibitory Effects ◽  
Renal Proximal Tubules ◽  
Intracellular Ca ◽  
Altered Response ◽  
Isolated Renal Tubule ◽  
Convoluted Tubules

Using a glucose microassay and in vitro isolated renal tubule perfusion technique, we have studied the actions of parathyroid hormone (PTH) on gluconeogenesis (GNG) and fluid (Jv) and phosphate (Jp) transport rates in isolated rabbit renal proximal tubules. In proximal straight tubules (PST), PTH stimulated GNG and inhibited Jv and Jp. In proximal convoluted tubules (PCT), PTH inhibited Jv but failed to affect GNG and Jp. An increase in Ca concentration, however, stimulated GNG and allowed PTH to inhibit Jp in PCT. Addition of the intracellular Ca antagonists trifluoperazine and N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7) abolished the inhibitory effects of PTH on Jv and Jp in both PCT and PST. In conclusion, these studies suggest that Ca-dependent intracellular pathways may be involved in the actions of PTH in rabbit renal proximal tubules. The altered response to PTH in rabbit PCT may be due to alterations in the response of intracellular Ca to the hormone.

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