Short-term stimulation of cellular autophagy by furosemide in the thick ascending limb of Henle's loop in the rat kidney

1988 ◽  
Vol 253 (3) ◽  
Author(s):  
Marcel Bahro ◽  
Gabriele Gertig ◽  
Ulrich Pfeifer
Keyword(s):  
Rat Kidney ◽  
Thick Ascending Limb ◽  
Short Term ◽  
Henle's Loop ◽  
Cellular Autophagy ◽  
Stimulation Of

Localization of rat CLC-K2 chloride channel mRNA in the kidney

1999 ◽  
Vol 276 (4) ◽  
pp. F552-F558 ◽  
Author(s):  
Momono Yoshikawa ◽  
Shinichi Uchida ◽  
Atsushi Yamauchi ◽  
Akiko Miyai ◽  
Yujiro Tanaka ◽  
...  
Keyword(s):  
In Situ Hybridization ◽  
Chloride Channel ◽  
Rat Kidney ◽  
Water Channel ◽  
Physiological Role ◽  
Thick Ascending Limb ◽  
Nephron Segments ◽  
Henle's Loop ◽  
Collecting Ducts

To gain insight into the physiological role of a kidney-specific chloride channel, CLC-K2, the exact intrarenal localization was determined by in situ hybridization. In contrast to the inner medullary localization of CLC-K1, the signal of CLC-K2 in our in situ hybridization study was highly evident in the superficial cortex, moderate in the outer medulla, and absent in the inner medulla. To identify the nephron segments where CLC-K2 mRNA was expressed, we performed in situ hybridization of CLC-K2 and immunohistochemistry of marker proteins (Na+/Ca2+exchanger, Na+-Cl−cotransporter, aquaporin-2 water channel, and Tamm-Horsfall glycoprotein) in sequential sections of a rat kidney. Among the tubules of the superficial cortex, CLC-K2 mRNA was highly expressed in the distal convoluted tubules, connecting tubules, and cortical collecting ducts. The expression of CLC-K2 in the outer and inner medullary collecting ducts was almost absent. In contrast, a moderate signal of CLC-K2 mRNA was observed in the medullary thick ascending limb of Henle’s loop, but the signal in the cortical thick ascending limb of Henle’s loop was low. These results clearly demonstrated that CLC-K2 was not colocalized with CLC-K1 and that its localization along the nephron segments was relatively broad compared with that of CLC-K1.

Phospholipase A2 is involved in mediating the effect of extracellular Ca2+ on apical K+ channels in rat TAL

1997 ◽  
Vol 273 (3) ◽  
pp. F421-F429 ◽  
Author(s):  
W. Wang ◽  
M. Lu ◽  
M. Balazy ◽  
S. C. Hebert
Keyword(s):  
Phospholipase A2 ◽  
Fluorescent Dyes ◽  
Rat Kidney ◽  
K Channel ◽  
Thick Ascending Limb ◽  
Channel Activity ◽  
Patch Clamp Technique ◽  
Acetoxymethyl Ester ◽  
K Channels ◽  
Stimulation Of

Raising extracellular Ca2+ (Ca2+o) stimulating the Ca(2+)-sensing receptor (CaR) decreased the activity of the apical 70-pS K+ channel via a cytochrome P-450-dependent mechanism in the thick ascending limb (TAL) of the rat kidney [W. H. Wang, M. Lu, and S. C. Hebert. Am. J. Physiol. 270 (Cell Physiol. 39): C103-C111, 1996]. We have now used the patch-clamp technique and fluorescent dyes to investigate the signaling mechanism by which this effect is produced. Addition of 500 microM gadolinium (Gd3+), an agent which has been shown to activate the CaR (E. M. Brown, G. Gamba, D. Riccardi, M. Lombardi, R. Butters, O. Kifor, A. Sun, M. A. Hediger, J. Lytton, and S. C. Hebert. Nature 366: 575-580, 1993), mimics the inhibitory effect of raising Ca2+o from 1.1 to 5 mM on channel activity. Effects of the high Ca2+o and Gd3+ were abolished by blockade of phospholipase A2 (PLA2) but not by inhibition of phospholipase C (PLC). Raising Ca2+o also increased 20-hydroxyeicosatetraenoic acid production significantly. To investigate the effect of stimulation of the CaR on intracellular Ca2+ (Ca2+i), we used the acetoxymethyl ester of fura 2 to monitor the Ca2+i. Raising Ca2+o from 1.1 to 5 mM increased the Ca2+i significantly from 50 to 150 nM. However, addition of thapsigargin failed to abolish the effect of 5 mM Ca2+o on Ca2+i. Also, application of Gd3+ only slightly increased the Ca2+i, suggesting that elevation of the Ca2+i by high Ca2+o was the result of an influx of Ca2+ rather than enhanced Ca2+ release from Ca2+ stores. That the increase in Ca2+ influx is not mainly responsible for the effect of stimulating the CaR on channel activity is further supported by experiments in which 500 microM Gd3+ inhibited the K+ channel in cell-attached patches in a Ca(2+)-free bath. Furthermore, addition of 500 microM Gd3+ or 5 mM Ca2+o decreased intracellular Na+ measured with fluorescent sodium indicator, suggesting inhibition of Na+ transport. We conclude that PLA2 is involved in the stimulation of the CaR-induced inhibition of apical K+ channels in the TAL.

scholarly journals Renal Na+-K+-Cl− cotransporter activity and vasopressin-induced trafficking are lipid raft-dependent

2008 ◽  
Vol 295 (3) ◽  
pp. F789-F802 ◽  
Author(s):  
Pia Welker ◽  
Alexandra Böhlick ◽  
Kerim Mutig ◽  
Michele Salanova ◽  
Thomas Kahl ◽  
...  
Keyword(s):  
Rat Kidney ◽  
Integral Membrane Protein ◽  
Surface Expression ◽  
Cholesterol Depletion ◽  
Xenopus Laevis Oocytes ◽  
Thick Ascending Limb ◽  
Short Term ◽  
Nacl Transport ◽  
Triton X

Apical bumetanide-sensitive Na+-K+-2Cl− cotransporter (NKCC2), the kidney-specific member of a cation-chloride cotransporter superfamily, is an integral membrane protein responsible for the transepithelial reabsorption of NaCl. The role of NKCC2 is essential for renal volume regulation. Vasopressin (AVP) controls NKCC2 surface expression in cells of the thick ascending limb of the loop of Henle (TAL). We found that 40–70% of Triton X-100-insoluble NKCC2 was present in cholesterol-enriched lipid rafts (LR) in rat kidney and cultured TAL cells. The related Na+-Cl− cotransporter (NCC) from rat kidney was distributed in LR as well. NKCC2-containing LR were detected both intracellularly and in the plasma membrane. Bumetanide-sensitive transport of NKCC2 as analyzed by 86Rb+ influx in Xenopus laevis oocytes was markedly reduced by methyl-β-cyclodextrin (MβCD)-induced cholesterol depletion. In TAL, short-term AVP application induced apical vesicular trafficking along with a shift of NKCC2 from non-raft to LR fractions. In parallel, increased colocalization of NKCC2 with the LR ganglioside GM1 and their polar translocation were assessed by confocal analysis. Apical biotinylation showed twofold increases in NKCC2 surface expression. These effects were blunted by mevalonate-lovastatin/MβCD-induced cholesterol deprivation. Collectively, these findings demonstrate that a pool of NKCC2 distributes in rafts. Results are consistent with a model in which LR mediate polar insertion, activity, and AVP-induced trafficking of NKCC2 in the control of transepithelial NaCl transport.

Stimulation of Na+/K+-ATPase activity by polyamines in the rat renal medullary cells of the thick ascending limb of Henle's loop

1990 ◽  
Vol 127 (3) ◽  
pp. 377-382 ◽  
Author(s):  
J. A. Charlton ◽  
P. H. Baylis
Keyword(s):  
Atpase Activity ◽  
Arginine Vasopressin ◽  
Thick Ascending Limb ◽  
Stimulus Response ◽  
Spermine Synthase ◽  
Medullary Thick Ascending Limb ◽  
Henle's Loop ◽  
Specific Inhibitors ◽  
Stimulation Of

ABSTRACT Previous studies have indicated that ornithine decarboxylase (ODC) may be involved in the stimulation of Na+/K+-ATPase activity by arginine vasopressin (AVP) in the rat renal medullary thick ascending limb of Henle's loop. The present study was aimed at establishing the role of the polyamines, the conversion products of ODC activity, in the stimulation of Na+/K+-ATPase by AVP. Using cytochemical methods, we have demonstrated an increase in Na+/K+-ATPase activity after stimulation with putrescine, spermidine and spermine (each 1 mmol/l) for 2·5,2 and 1·5 min respectively. The specific inhibitors of spermidine and spermine synthase, bis-cyclohexylammonium sulphate and N-alkylated-1,3-diaminopropane respectively, inhibited the stimulation of Na+/K+-ATPase by AVP, this inhibition being reversed by spermine. These findings suggest that polyamines are involved in the stimulus-response coupling of the hormone-mediated response. Journal of Endocrinology (1990) 127, 377–382

Stimulation of rat renal medullary Na+/K+-ATPase by arginine vasopressin is mediated by the V2 receptor

1990 ◽  
Vol 127 (2) ◽  
pp. 213-216 ◽  
Author(s):  
J. A. Charlton ◽  
P. H. Baylis
Keyword(s):  
Atpase Activity ◽  
Arginine Vasopressin ◽  
Thick Ascending Limb ◽  
Medullary Thick Ascending Limb ◽  
Henle's Loop ◽  
Cytochemical Bioassay ◽  
V2 Receptor ◽  
Stimulation Of

ABSTRACT In previous studies, we have demonstrated that 1–10 fmol arginine vasopressin (AVP)/l maximally stimulates the activity of the enzyme Na+/K+-ATPase in the rat renal medullary thick ascending limb (MTAL) of Henle's loop after 4 or 10 min of stimulation when measured using a cytochemical bioassay. We have tested the hypothesis that this stimulation is mediated by the V2 receptor in the MTAL. A cytochemical bioassay was used to investigate the effect of specific V1 and V2/V1 antagonists and a synthetic V2 agonist [1-deamino,8-d-arginine]-vasopressin (dDAVP), on the activity of Na+/K+-ATPase. There was no effect of the V1 antagonist (1 fmol-1 μmol/l) in inhibiting the activity of Na+/K+-ATPase stimulated by 1 fmol AVP/l. In contrast, 100 pmol of the V2/V1 antagonist/l significantly (P < 0·001) inhibited the stimulation of Na+/K+-ATPase activity by 1 fmol AVP/l from 55·5±4·3 (s.e.m.) to 31·9±1·6 mean integrated extinction (MIE) after 4 min of stimulation and from 67·0±3·2 to 36·9±0·7 MIE after 10 min of stimulation. Similarly, the stimulation of Na+/K+-ATPase by 10 fmol dDAVP/l was inhibited by the V2/V1 antagonist from 55·1±1·0 to 26·1±0·5 MIE after 4 min of stimulation. We conclude that the stimulation of Na+/K+-ATPase by AVP is mediated by the V2 receptor in the rat renal MTAL. Journal of Endocrinology (1990) 127, 213–216

31P nuclear magnetic resonance study of steady-state adenosine 5′-triphosphate levels during graded hypoxia in the isolated perfused rat kidney

1988 ◽  
Vol 74 (4) ◽  
pp. 437-448 ◽  
Author(s):  
P. J. Ratcliffe ◽  
Z. H. Endre ◽  
S. J. Scheinman ◽  
J. D. Tange ◽  
J. G. G. Ledingham ◽  
...  
Keyword(s):  
Steady State ◽  
Proximal Tubule ◽  
Oxygen Delivery ◽  
Rat Kidney ◽  
Thick Ascending Limb ◽  
Cellular Injury ◽  
Isolated Perfused Rat Kidney ◽  
Medullary Thick Ascending Limb ◽  
Henle's Loop ◽  
Perfused Rat Kidney

1. A model of controlled hypoxia in the isolated perfused rat kidney has been used to compare the extent of reduction in the steady-state level of adenosine 5′-triphosphate (ATP) from that initially observed with alterations in renal function and with the development of tubular cell injury. 2. ATP depletion was observed in response to decreased total oxygen delivery even when delivery greatly exceeded consumption and the venous oxygen tension remained in excess of 150 mmHg. 3. Increases in the fractional excretion of sodium occurred progressively below an apparent threshold value of whole kidney ATP of approximately 80% of the baseline. 4. With modestly decreased oxygen delivery, cellular injury was confined to deep proximal tubule and medullary thick ascending limb of Henle's loop. Severely decreased oxygen delivery rates were associated with cellular damage spreading throughout the cortex. 5. Even the smallest reductions in whole kidney ATP were associated with morphological damage to tubular cells. The extent of reduction in whole kidney ATP was closely correlated and approximately equivalent to the calculated volume of injured cells. 6. Our results indicate that reduction in whole kidney ATP during decreased oxygen delivery is a valid marker of the extent of injurious cellular hypoxia and are consistent with the view that cellular ATP concentrations in hypoxia are markedly inhomogeneous. They support the hypothesis that specific regions of the perfused kidney become critically hypoxic and develop cellular injury while overall oxygen delivery remains high. Areas at risk include deep proximal tubule as well as the medullary thick ascending limb of Henle's loop.

Production of superoxide through NADH oxidase in thick ascending limb of Henle's loop in rat kidney

2002 ◽  
Vol 282 (6) ◽  
pp. F1111-F1119 ◽  
Author(s):  
Ningjun Li ◽  
Fu-Xian Yi ◽  
Jamie L. Spurrier ◽  
Carol A. Bobrowitz ◽  
Ai-Ping Zou
Keyword(s):  
Nadh Oxidase ◽  
Rat Kidney ◽  
Renal Tissue ◽  
Oxidase Inhibitor ◽  
Thick Ascending Limb ◽  
Metabolizing Enzymes ◽  
Text Production ◽  
Henle's Loop ◽  
Nadh Oxidase Activity ◽  
Oxide Synthase

We recently reported that NADH oxidase is one of the major enzymes responsible for superoxide (O[Formula: see text]·) production in the rat kidney. However, the functional significance of NADH oxidase-mediated O[Formula: see text]· production and the mechanisms regulating this enzyme activity are poorly understood. Using fluorescence microscopic imaging analysis, the present study demonstrated that thick ascending limbs of Henle's loop (TALHs) exhibited red fluorescence when incubated with dihydroethidium (DHE), suggesting that O[Formula: see text]· is produced in this tubular segment. Compared with other nephron segments, TALHs from both renal cortex and medulla showed the highest fluorescence intensity. By incubating cortical TALHs (cTALHs) with the substrates of NADH oxidase, xanthine oxidase, nitric oxide synthase, arachidonic acid-metabolizing enzymes, and intramitochondrial oxidases, NADH oxidase was found to be one of the most important enzymes for O[Formula: see text]· production in this tubular segment. The NADH oxidase inhibitor diphenyleneiodonium (DPI; 100 μM) completely blocked NADH-induced O[Formula: see text]· production in cTALHs. Exposure of cTALHs to low Po2(5–10 Torr) significantly increased O[Formula: see text]· production regardless of the absence or presence of NADH. Furthermore, angiotensin II (100 nM) increased NADH oxidase activity by 32%, which was completely blocked by DPI. These results suggest that NADH oxidase is a major enzyme responsible for O[Formula: see text]· production in the TALHs and that the production of O[Formula: see text]· via NADH oxidase may be regulated by renal tissue oxygenation and circulating hormones.

Effect of PTH on calcium transport across the cortical thick ascending limb of Henle's loop

1980 ◽  
Vol 239 (2) ◽  
pp. F121-F126 ◽  
Author(s):  
J. E. Bourdeau ◽  
M. B. Burg
Keyword(s):  
Adrenocorticotropic Hormone ◽  
Calcium Absorption ◽  
Calcium Flux ◽  
Thick Ascending Limb ◽  
Henle's Loop ◽  
Transepithelial Voltage ◽  
Net Flux ◽  
Stimulation Of

Cortical thick ascending limbs of Henle's loop were dissected from rabbit kidneys and perfused in vitro. Unidirectional transepithelial calcium fluxes from lumen-to-bath and bath-to-lumen were measured with 45Ca. The tubules were bathed in 150 mM sodium and perfused with 60 mM sodium to simulate conditions in the cortical thick ascending limb in vivo. During the 20-30 min preceding the addition of parathyroid hormone (PTH), net calcium absorption decreased from 0.207 to 0.084 pmol x s-1 x cm-1. After addition of synthetic bovine PTH (60-64 nM) to the bath, there was an immediate increase in calcium absorption, and by 20 min the net flux increased to 0.415 pmol x s-1 x cm-1. The increase in calcium absorption was due to an increase in the lumen-to-bath flux. Dibutyryl-cAMP or 8-BrcAMP mimicked PTH; adrenocorticotropic hormone had no effect on the calcium flux. Transepithelial voltage was unchanged after addition of PTH. We conclude that PTH increases calcium absorption across the cortical thick ascending limb, probably by stimulation of adenylate cyclase.

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