Indomethacin and sodium retention in the rat: role of inhibition of prostaglandin E2 synthesis

1992 ◽  
Vol 83 (3) ◽  
pp. 307-311 ◽  
Author(s):  
Pnina Scherzer ◽  
Hanna Wald ◽  
Dvora Rubinger ◽  
Mordecai M. Popovtzer
Keyword(s):  
Atpase Activity ◽  
Prostaglandin E2 ◽  
Collecting Duct ◽  
Proximal Convoluted Tubule ◽  
Distal Convoluted Tubule ◽  
Thick Ascending Limb ◽  
Cortical Collecting Duct ◽  
Straight Tubule ◽  
Medullary Thick Ascending Limb ◽  
Proximal Straight Tubule

1. To further explore the Na+-retaining effect of indomethacin along the whole length of the nephron, the Na+-K+-ATPase activity of isolated tubules from indomethacin-pretreated rats was compared with that of tubules isolated from intact rats and exposed directly to prostaglandin E2. 2. Indomethacin increased Na+-K+-ATPase activity in the proximal convoluted tubule (+24%, P<0.001 versus control), proximal straight tubule (+75%, P<0.001 versus control), medullary thick ascending limb (+68%, P<0.001 versus control), cortical thick ascending limb (+7%, not significant) and cortical collecting duct (+18%, P<0.025 versus control). In contrast, in the distal convoluted tubule indomethacin decreased Na+-K+-ATPase activity by −42% (P<0.001 versus control). 3. Indomethacin also strongly increased Na+-K+-ATPase activity in the cortical collecting duct of adrenalectomized rats. 4. In isolated tubules from control rats, prostaglandin E2 reduced Na+-K+-ATPase activity in the proximal convoluted tubule (−33%, P<0.05), proximal straight tubule (−60%, P<0.001), medullary thick ascending limb (−43%, P<0.001), cortical thick ascending limb (−25%, P<0.001) and cortical collecting duct (−45%, P<0.001) and in the distal convoluted tubule, prostaglandin E2 increased Na+-K+-ATPase activity (+32%, P<0.05). 5. That these changes in Na+-K+-ATPase activity in indomethacin-pretreated rats and prostaglandin E2-treated controls are similar in magnitude but occur in opposite directions suggests that the response to indomethacin is mediated by inhibition of prostaglandin E2 synthesis in the nephron. In the cortical collecting duct the effect of indomethacin is aldosterone-independent.

Enhanced glomerular filtration and Na+-K+-ATPase with furosemide administration

1987 ◽  
Vol 252 (5) ◽  
pp. F910-F915 ◽  
Author(s):  
P. Scherzer ◽  
H. Wald ◽  
M. M. Popovtzer
Keyword(s):  
Glomerular Filtration ◽  
Collecting Duct ◽  
Thick Ascending Limb ◽  
Cortical Collecting Duct ◽  
Nephron Segments ◽  
Medullary Thick Ascending Limb ◽  
Henle's Loop ◽  
Proximal Straight Tubule ◽  
X 24 ◽  
Furosemide Administration

To evaluate the effect of furosemide on kidney function, glomerular filtration rate (GFR), urinary Na excretion (UNaV), Na reabsorption (NAR), and Na+-K+-ATPase in isolated nephron segments were measured in 1) rats treated with furosemide 10 mg X 100 g-1 X 24 h-1 ip for 7 days, and 2) rats receiving an oral Na load for 12 days. In furosemide-treated rats, GFR rose from 0.61 +/- 0.03 (mean +/- SD) to 0.83 +/- 0.06 ml/min (P less than 0.01), UNaV rose from 904 +/- 71 to 1,402 +/- 85 mueq/day (P less than 0.001), and net NAR rose from 87.5 +/- 3.7 to 116.7 +/- 9.0 mueq/min (P less than 0.01). Na+-K+-ATPase remained unchanged in the proximal convoluted tubule (PCT), proximal straight tubule (PST), cortical thick ascending limb of Henle's loop (cTALH), and medullary thick ascending limb of Henle's loop (mTALH), but was increased in the distal convoluted tubule (DCT) and in cortical collecting duct (CCD) from 48.5 +/- 1.2 to 75.3 +/- 0.7 (P less than 0.001) and from 18.6 +/- 0.7 to 27.1 +/- 2.7 (P less than 0.02) X 10(-11) mol X mm-1 X min-1, respectively. In Na-loaded rats GFR rose from 0.61 +/- 0.04 to 0.86 +/- 0.03 ml/min (P less than 0.001), UNaV rose from 1,064 +/- 118 to 18,532 +/- 2,045 mueq/day (P less than 0.001), net NAR from 88.1 +/- 3.0 to 107.8 +/- 3.9 mueq/min and Na-K-ATPase in the mTALH rose from 40.3 +/- 1.4 to 56.2 +/- 2.11 (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Insulin Unresponsiveness of Tubular Monovalent Cation Transport during Fructose-Induced Hypertension in Rats

1995 ◽  
Vol 88 (3) ◽  
pp. 293-299 ◽  
Author(s):  
Eric Féraille ◽  
Sophie Marsy ◽  
Catherine Barlet-Bas ◽  
Martine Rousselot ◽  
Lydie Cheval ◽  
...  
Keyword(s):  
Collecting Duct ◽  
Insulin Binding ◽  
Cation Transport ◽  
Proximal Convoluted Tubule ◽  
Sodium Reabsorption ◽  
Thick Ascending Limb ◽  
Cortical Collecting Duct ◽  
Hypertensive Rats ◽  
Medullary Thick Ascending Limb ◽  
Sodium Handling

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. 4. We conclude that hypertension developed in rats fed a fructose-enriched diet regardless of change in renal sodium handling since (1) the basal tubular sodium reabsorption capacity of the nephron remained unchanged and (2) the response of the tubular cation transport to insulin was abolished. These results strongly argue against the participation of insulin-mediated tubular sodium retention in the pathogenesis of hypertension and suggest that insulin-related mechanisms modulate the blood vessel reactivity.

NEM-sensitive ATPase activity in rat nephron: effect of metabolic acidosis and alkalosis

1990 ◽  
Vol 258 (2) ◽  
pp. F297-F304 ◽  
Author(s):  
S. Sabatini ◽  
M. E. Laski ◽  
N. A. Kurtzman
Keyword(s):  
Enzyme Activity ◽  
Metabolic Acidosis ◽  
Atpase Activity ◽  
Collecting Duct ◽  
Proximal Convoluted Tubule ◽  
Thick Ascending Limb ◽  
Cortical Collecting Duct ◽  
Chronic Metabolic Acidosis ◽  
Collecting Tubule ◽  
Cortical Collecting Tubule

The present study was designed to quantitate the amount and to map the localization of N-ethylmaleimide (NEM)-sensitive adenosinetriphosphatase (ATPase) activity in microdissected segments of the rat nephron. After complete nephron mapping the effect of chronic metabolic acidosis and alkalosis on enzyme activity was determined. In control animals the highest enzyme activity was found in the early proximal convoluted tubule of juxtamedullary nephrons; superficial early proximal tubule as well as medullary and cortical thick ascending limbs and collecting ducts also contained substantial activity. Enzyme activity in the papillary collecting duct before entry into the ducts of Bellini was 329 +/- 93 pmol.mm-1.h-1 (n = 8); after entry, however, enzyme activity was approximately one-fourth that value (60 +/- 9 pmol.mm-1.h-1, n = 8, P less than 0.01). No NEM-sensitive ATPase activity was found in the thin limbs of the loop of Henle. Enzyme activity increased in both the medullary and cortical thick ascending limbs as well as in the cortical collecting tubule in response to NH4Cl-induced chronic metabolic acidosis; in the cortical collecting duct, metabolic acidosis increased maximum activity (Vmax) but did not change Michaelis-Menten constant (Km). In the proximal convoluted tubule, enzyme activity decreased with metabolic acidosis. Bicarbonate loading had no effect on enzyme activity except in the most distal portion of the collecting duct where it was stimulated. These results show that NEM-sensitive ATPase activity exists throughout much of the rat nephron. These data suggest that both the cortical collecting tubule and thick ascending limb are regulatory sites of distal urinary acidification during acid loading.

Regional and segmental localization of AE2 anion exchanger mRNA and protein in rat kidney

1995 ◽  
Vol 269 (4) ◽  
pp. F461-F468 ◽  
Author(s):  
F. C. Brosius ◽  
K. Nguyen ◽  
A. K. Stuart-Tilley ◽  
C. Haller ◽  
J. P. Briggs ◽  
...  
Keyword(s):  
Collecting Duct ◽  
Rat Kidney ◽  
Chloride Concentration ◽  
Transepithelial Transport ◽  
Thick Ascending Limb ◽  
Cortical Collecting Duct ◽  
Base Exchange ◽  
Medullary Thick Ascending Limb ◽  
Nephron Segment ◽  
Medullary Collecting Duct

Chloride/base exchange activity has been detected in every mammalian nephron segment in which it has been sought. However, in contrast to the Cl-/HCO3- exchanger AE1 in type A intercalated cells, localization of AE2 within the kidney has not been reported. We therefore studied AE2 expression in rat kidney. AE2 mRNA was present in cortex, outer medulla, and inner medulla. Semiquantitative polymerase chain reaction of cDNA from microdissected tubules revealed AE2 cDNA levels as follows [copies of cDNA derived per mm tubule (+/- SE)]: proximal convoluted tubule, 688 +/- 161; proximal straight tubule, 652 +/- 189; medullary thick ascending limb, 1,378 +/- 226; cortical thick ascending limb, 741 +/- 24; cortical collecting duct, 909 +/- 71; and outer medullary collecting duct, 579 +/- 132. AE2 cDNA was also amplified in thin limbs and in inner medullary collecting duct. AE2 polypeptide was detected in all kidney regions. AE2 mRNA and protein were also detected in several renal cell lines. The data are compatible with the postulated roles of AE2 in maintenance of intracellular pH and chloride concentration and with its possible participation in transepithelial transport.

AVP-stimulated nucleotide secretion in perfused mouse medullary thick ascending limb and cortical collecting duct

2009 ◽  
Vol 297 (2) ◽  
pp. F341-F349 ◽  
Author(s):  
Elvin Odgaard ◽  
Helle A. Praetorius ◽  
Jens Leipziger
Keyword(s):  
Collecting Duct ◽  
Tubular Secretion ◽  
Hormonal Control ◽  
Similar Response ◽  
Thick Ascending Limb ◽  
Cortical Collecting Duct ◽  
Medullary Thick Ascending Limb ◽  
Tubular Transport ◽  
Renal Tubular Transport ◽  
Renal Tubular

Extracellular nucleotides are local, short-lived signaling molecules that inhibit renal tubular transport via both luminal and basolateral P2 receptors. Apparently, the renal epithelium itself is able to release nucleotides. The mechanism and circumstances under which nucleotide release is stimulated remain elusive. Here, we investigate the phenomenon of nucleotide secretion in intact, perfused mouse medullary thick ascending limb (mTAL) and cortical collecting duct (CCD). The nucleotide secretion was monitored by a biosensor adapted to register nucleotides in the tubular outflow. Intracellular Ca2+ concentration ([Ca2+]i) was measured simultaneously in the biosensor cells and the renal tubule with fluo 4. We were able to identify spontaneous tubular nucleotide secretion in resting perfused mTAL. In this preparation, 10 nM AVP and 1-desamino-8-d-arginine vasopressin (dDAVP) induced robust [Ca2+]i oscillations, whereas AVP in the CCD induced large, slow, and transient [Ca2+]i elevations. Importantly, we identify that AVP/dDAVP triggers tubular secretion of nucleotides in the mTAL. After addition of AVP/dDAVP, the biosensor registered bursts of nucleotides in the tubular perfusate, corresponding to a tubular nucleotide concentration of ∼0.2–0.3 μM. A very similar response was observed after AVP stimulation of CCDs. Thus AVP stimulated tubular secretion of nucleotides in a burst-like pattern with peak tubular nucleotide concentrations in the low-micromolar range. We speculate that local nucleotide signaling is an intrinsic feedback element of hormonal control of renal tubular transport.

Different mechanisms of renal Na-K-ATPase regulation by protein kinases in proximal and distal nephron

1993 ◽  
Vol 265 (3) ◽  
pp. F399-F405 ◽  
Author(s):  
T. Satoh ◽  
H. T. Cohen ◽  
A. I. Katz
Keyword(s):  
Arachidonic Acid ◽  
Protein Kinase ◽  
Collecting Duct ◽  
Common Mechanism ◽  
Thick Ascending Limb ◽  
Cortical Collecting Duct ◽  
Distal Nephron ◽  
Inhibitory Peptide ◽  
Medullary Thick Ascending Limb ◽  
Pump Activity

We recently reported a novel intracellular mechanism of Na-K-adenosinetriphosphatase (Na-K-ATPase) regulation in the cortical collecting duct (CCD) by agents that increase cell adenosine 3',5'-cyclic monophosphate (cAMP), which involves stimulation of protein kinase A (PKA) and phospholipase A2 (PLA2). We now determined whether this mechanism also operates in other nephron segments. In the medullary thick ascending limb (MTAL) dopamine, the DA1 agonist fenoldopam, forskolin, or dibutyryl-cAMP inhibited Na-K-ATPase activity, similar to results in CCD. In both segments this effect was blocked by 20-residue inhibitory peptide (IP20), a peptide inhibitor of PKA, but not by staurosporine, a protein kinase C (PKC) inhibitor. PKC activators phorbol 12-myristate 13-acetate, phorbol 12,13-dibutyrate, and 1,2-myristate 13-acetate, phorbol 12,13-dibutyrate, and 1,2-dioctanoylglycerol had no effect on Na-K pump activity in either CCD or MTAL. In contrast, all three PKC activators inhibited pump activity in the proximal convoluted tubule (PCT), an effect reproduced only by dopamine or by parathyroid hormone [PTH-(1-34)]. In PCT the pump inhibition by dopamine or PTH-(1-34) was abolished by staurosporine but not by IP20. The PLA2 inhibitor mepacrine prevented the effect of all agents, and arachidonic acid produced a dose-dependent pump inhibition in each of the three segments studied. We conclude that intracellular mechanisms of Na-K-ATPase regulation differ along the nephron, as they involve activation of PKA in CCD and MTAL and of PKC in PCT. These two pathways probably share a common mechanism in stimulating PLA2, arachidonic acid release, and production of eicosanoids in both the proximal and distal nephron.

Localization of the extracellular Ca(2+)-sensing receptor and PTH/PTHrP receptor in rat kidney

1996 ◽  
Vol 271 (4) ◽  
pp. F951-F956 ◽  
Author(s):  
D. Riccardi ◽  
W. S. Lee ◽  
K. Lee ◽  
G. V. Segre ◽  
E. M. Brown ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Collecting Duct ◽  
Rat Kidney ◽  
Physiological Role ◽  
Urinary Concentration ◽  
Thick Ascending Limb ◽  
Cortical Collecting Duct ◽  
Medullary Thick Ascending Limb ◽  
Parathyroid Hormone Related Protein ◽  
Pthrp Receptor

Using a strategy based on homology to the bovine parathyroid Ca(2+)-sensing receptor previously identified by us (5), we have recently isolated an extracellular, G protein-coupled Ca2+/ polyvalent cation-sensing receptor, RaKCaR (22), from rat kidney. The localization and physiological role(s) of this receptor in the kidney are not well understood. In the present study, we assessed the distribution of mRNAs for RaKCaR and the parathyroid hormone/parathyroid hormone-related protein (PTH/PTHrP) receptor along the rat nephron by in situ hybridization and reverse transcriptase-polymerase chain reaction of microdissected nephron segments. Our results show that transcripts for both receptors coexpress at glomeruli, proximal convoluted tubule, proximal straight tubule, cortical thick ascending limb, distal convoluted tubule, and cortical collecting duct. In addition, RaKCaR (but not PTH/PTHrP receptor) transcripts were found in the medullary thick ascending limb and outer medullary and inner medullary collecting ducts. These findings raise the possibility of roles for RaKCaR not only in the regulation of divalent mineral reabsorption but also in water reabsorption and urinary concentration. Taken together, our results provide new insights in understanding the effects of hypercalcemia on hormone-stimulated salt and water transport.

Cl− channels in basolateral renal medullary membranes XII. Anti-rbClC-Ka antibody blocks MTAL Cl−channels

1997 ◽  
Vol 273 (6) ◽  
pp. F1030-F1038 ◽  
Author(s):  
Christopher J. Winters ◽  
Ludwika Zimniak ◽  
W. Brian Reeves ◽  
Thomas E. Andreoli
Keyword(s):  
Lipid Bilayers ◽  
Collecting Duct ◽  
Basolateral Membrane ◽  
Rabbit Kidney ◽  
Thick Ascending Limb ◽  
Cortical Collecting Duct ◽  
Patch Clamp Technique ◽  
Medullary Thick Ascending Limb ◽  
Acid Fragment ◽  
Cl Channels

Cl− channels in the medullary thick ascending limb (MTAL) studied by either patch-clamp technique or reconstitution into lipid bilayers are activated by increases in intracellular Cl−concentrations. rbClC-Ka, a ClC Cl− channel, may represent this channel. We therefore evaluated the role of rbClC-Ka in transcellular MTAL Cl− transport in two separate ways. First, an antibody was raised against a fusion protein containing a 153-amino acid fragment of rbClC-Ka. Immunostaining of rabbit kidney sections with the antibody was localized to basolateral regions of MTAL and cortical thick ascending limb (CTAL) segments and also to the cytoplasm of intercalated cells in the cortical collecting duct. Second, Cl− uptake and efflux were measured in suspensions of mouse MTAL segments. Cl− uptake was bumetanide sensitive and was stimulated by treatment with a combination of vasopressin + forskolin + dibutyryl adenosine 3′,5-cyclic monophosphate (DBcAMP). Cl− efflux was also increased significantly by vasopressin + forskolin + DBcAMP from 114 ± 20 to 196 ± 36 nmol ⋅ mg protein−1 ⋅ 45 s−1( P = 0.003). Cl− efflux was inhibited by the Cl− channel blocker diphenylamine-2-carboxylate (154 ± 26 vs. 70 ± 21 nmol ⋅ mg protein−1 ⋅ 45 s−1, P = 0.003). An anti-rbClC-Ka antibody, which inhibits the activity of MTAL Cl− channels in lipid bilayers, reduced Cl− efflux from intact MTAL segments (154 ± 28 vs. 53 ± 14 nmol ⋅ mg protein−1 ⋅ 45 s−1, P = 0.02). These results support the view that rbClC-Ka is the basolateral membrane Cl− channel that mediates vasopressin-stimulated net Cl− transport in the MTAL segment.

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