THE EFFECT OF DAMAGE TO VARIOUS PARTS OF THE RENAL TUBULE ON THE EXCRETION OF PHOSPHATE BY THE DOG'S KIDNEY

1959 ◽  
Vol 37 (1) ◽  
pp. 103-111 ◽  
Author(s):  
T. F. Nicholson ◽  
G. W. Shepherd

The first third of the proximal tubules of the left kidney in dogs was damaged by the injection of 2.5 mg% potassium dichromate, the last two thirds by the injection of 0.5% sodium tartrate, and the distal tubules by the retrograde injection up the ureter of 0.05% mercuric chloride. Damage to the first third of the proximal tubule resulted in marked increase in phosphate excretion. Damage to the last two thirds of the proximal tubule had no significant effect on the output of phosphate. When the distal tubule was damaged the excretion of phosphate was greatly reduced. The results indicate that phosphate is reabsorbed in the first third of the proximal tubule and actively excreted by the distal tubule.

1959 ◽  
Vol 37 (1) ◽  
pp. 103-111 ◽  
Author(s):  
T. F. Nicholson ◽  
G. W. Shepherd

The first third of the proximal tubules of the left kidney in dogs was damaged by the injection of 2.5 mg% potassium dichromate, the last two thirds by the injection of 0.5% sodium tartrate, and the distal tubules by the retrograde injection up the ureter of 0.05% mercuric chloride. Damage to the first third of the proximal tubule resulted in marked increase in phosphate excretion. Damage to the last two thirds of the proximal tubule had no significant effect on the output of phosphate. When the distal tubule was damaged the excretion of phosphate was greatly reduced. The results indicate that phosphate is reabsorbed in the first third of the proximal tubule and actively excreted by the distal tubule.


1984 ◽  
Vol 246 (2) ◽  
pp. F155-F158
Author(s):  
A. Haramati ◽  
J. A. Haas ◽  
F. G. Knox

We evaluated the response of superficial and deep nephron proximal tubules to PTH in thyroparathyroidectomized (TPTX) rats fed a normal phosphate diet (0.7%). As phosphate reabsorption is not detectable in the ascending limb of the loop of Henle, fractional phosphate delivery (FDPi%) to the superficial early distal tubule and papillary loop of Henle reflects delivery from superficial and deep nephron proximal tubules, respectively. Re-collection micropuncture experiments were performed in nine acutely TPTX rats before and after the infusion of PTH (33 U/kg bolus; 1 U X kg-1 X min-1). In response to PTH, fractional phosphate excretion increased from 3.3 to 26.2% (P less than 0.05). FDPi% was less from the deep than from the superficial proximal tubule (5.7 vs. 15.7%, P less than 0.05) prior to PTH, indicating enhanced phosphate reabsorption by deep compared with superficial proximal tubules. During PTH infusion, FDPi% was increased in both nephron groups compared with control (P less than 0.05), but there were no differences in phosphate delivery between deep (28.0%) and superficial (29.7%) proximal tubules. We conclude that in acutely volume-expanded TPTX rats, infusion of a pharmacologic dose of PTH decreases phosphate reabsorption in both superficial and deep nephrons. Furthermore, the heterogeneity of FDPi% from deep compared with superficial proximal tubules seen in TPTX rats is absent during PTH infusion.


1999 ◽  
Vol 277 (1) ◽  
pp. F66-F74 ◽  
Author(s):  
D. E. Casarini ◽  
M. A. Boim ◽  
R. C. R. Stella ◽  
N. Schor

The activities of serine endopeptidase, prolyl endopeptidase and neutral endopeptidase were determined in tubular fluid collected from several portions of the rat nephron as well as in urine. The enzyme activities were measured by HPLC using bradykinin (BK) as substrate. Free residual peptides of BK obtained by the action of these enzymes on the locally produced BK were also determined. The endopeptidase activities were found to be present throughout the nephron. Equimolar fragments of BK were detected in the early proximal tubule (Arg1-Pro7, Phe8-Arg9, Arg1-Gly4, Phe5-Arg9, and BK), late proximal tubule (Arg1-Phe5, Arg1-Pro7, Gly4-Pro7, Gly4-Arg9, and BK), late distal tubule (Arg1-Gly4, Phe5-Arg9, Arg1-Phe5, Ser6-Arg9, Gly4-Arg9, BK, and [des-Arg9]BK) and urine (Phe8-Arg9, Phe5-Arg9, Arg1-Phe5, Ser6-Arg9, Arg1-Pro7, Gly4-Pro7, Gly4-Arg9, BK, and [des-Arg9]BK). Our data suggest that the endopeptidases and exopeptidases are secreted by the nephron. Early proximal tubules secrete angiotensin converting enzyme and neutral endopeptidase, differing from late distal tubules that produce prolyl endopeptidase, serine endopeptidase, carboxypeptidase, and also neutral endopeptidase. All enzymes detected along the rat nephron were found in the urine. The existence of endopeptidases and carboxypeptidase in the distal nephron may have a potential physiological role in the inactivation of the kinins formed by kallikrein in the kidney and also in the inactivation of additional peptides other than BK.


1983 ◽  
Vol 244 (3) ◽  
pp. F265-F269 ◽  
Author(s):  
A. Haramati ◽  
J. A. Haas ◽  
F. G. Knox

Dietary phosphate intake is now recognized to be a primary regulator of renal phosphate excretion. However, the nephron sites involved in the adaptation to changes in dietary phosphate are unclear. We tested the hypothesis that deep and superficial nephrons respond differently to changes in dietary phosphate by comparing fractional phosphate delivery (FDP%) from proximal tubules of both nephron populations. Because phosphate reabsorption is not detectable in the ascending loop of Henle, FDP% to the superficial early distal tubule and papillary loop of Henle reflect delivery from superficial and deep nephron proximal tubules, respectively. Micropuncture experiments were performed in 17 acutely TPTX rats fed either a low (0.07%) or a high (1.8%) phosphate diet for 4 days prior to the experiment. In low phosphate diet, fractional phosphate excretion was 0.93 +/- 0.26%. FDP% was 7.5 +/- 0.5 and 9.1 +/- 2.2% from superficial and deep nephron proximal tubules, respectively (P greater than 0.05). In high phosphate diet, fractional phosphate excretion was 29.6 +/- 5.0%. FDP% was significantly greater from superficial proximal tubules, 33.9 +/- 4.6%, compared with that from deep nephron proximal tubules, 14.0 +/- 2.7% (P less than 0.05). We conclude that significant adaptation of phosphate reabsorption in response to changes in dietary phosphate intake occurs in the superficial but not in the deep nephron proximal tubule in acutely TPTX volume-expanded rats. In addition, the presence of distal phosphate reabsorption was not evident in high phosphate diet but must occur in low phosphate diet.


1987 ◽  
Vol 65 (10) ◽  
pp. 2093-2098 ◽  
Author(s):  
Michèle G. Brunette ◽  
Sylvie Blouin ◽  
Meathan Chan

The purpose of this study was to investigate whether Ca2+–Mg2+ ATPase in the distal tubule (where calcium transport is active, against a gradient, and hormone dependent) presents some characteristics different from those observed in the proximal tubule, and whether these characteristics are likely to shed light on the respective roles of this enzyme at the two sites of the nephron. The Ca2+- and Mg2+-dependent ATP hydrolysis was measured in microdissected segments of the distal nephron, the kinetic parameters were determined, and the influence of magnesium upon the sensitivity to calcium was examined. Results were compared with those obtained in the proximal tubule, and in purified membranes as reported by others. In the distal tubule, low concentrations of Mg2+ (< 10−7 M) did not influence ATP hydrolysis. At concentrations above 10−7 M, Mg2+ increased ATP hydrolysis according to Michaelis kinetics (apparent Km = 11.3 ± 2.4 μM, Vmax = 219 ± 26 pmol∙mm−1∙20 min−1). The addition of 1 μM Ca2+ decreased the apparent Km for Mg2+ and the Vmax for Mg2+. Similar results were obtained in the proximal tubule. At low Mg2+ concentrations, Ca2+ also stimulated ATP hydrolysis according to Michaelis kinetics with an apparent Km value for Ca2+ of 0.18 ± 0.06 and 0.10 ± 0.03 μM Ca2+ (ns) and a Vmax of 101 ± 12 and 89 ± 9 pmol∙mm−1∙20 min−1 (ns) in the distal and proximal tubules, respectively. In the two segments, the addition of Mg2+ strongly decreased the sensitivity to 1 μM Ca2+ so that at 1 mM Mg2+, the Ca2+-dependent ATPase activity was at the limit of detection. In conclusion, the kinetic parameters of the Ca2+- and Mg2+-dependent ATP hydrolysis were similar at the two sites of the nephron, and were also similar to those reported for the enzyme present in purified basolateral membranes. The nonadditive effect of the two cations Ca2+ and Mg2+ suggests that the two ATPase activities belong to the same enzyme, and this enzyme is the same in the proximal and distal tubules. Differences in Ca2+ transport characteristics should be attributed to factors other than variations in the nature of the Ca2+–Mg2+ ATPase.


1957 ◽  
Vol 35 (1) ◽  
pp. 641-644
Author(s):  
T. F. Nicholson

The proximal tubules of the left kidney in dogs were damaged by the injection of 0.5% racemic sodium tartrate into the left renal artery. In other experiments the distal tubules were damaged by the injection of 0.05% mercuric chloride up the left ureter. In animals with proximal tubular damage, intravenous infusions of desoxycorticosterone or aldosterone which produced a significant drop in sodium excretion from the normal kidney had no effect on the amount of sodium excreted by the damaged kidney. In animals with distal tubular damage the effect of these hormones on the damaged kidney was as great as on the normal kidney.


1985 ◽  
Vol 63 (2) ◽  
pp. 155-158 ◽  
Author(s):  
A. D. Baines ◽  
R. Drangova ◽  
C. Hatcher

To locate the sites of dopamine (D) production in rat renal cortex, we separated glomeruli and proximal tubules by sieving or centrifugation in Percoll after collagenase digestion. After centrifugation layer I contained 60–80% glomeruli and 20–40% tubule fragments, half of which did not stain with alkaline phosphatase, layer II contained 0–5% glomeruli, 10–25% tubule fragments other than proximal tubules, and 70–85% proximal tubule fragments. Layer IV contained 85–95% proximal tubules. Gluconeogenic rates were (micromoles per hour per gram wet weight) as follows: I, 4 ± 1; II, 7 ± 2; and IV, 16 ± 1. Norepinephrine (NE) content was (picomoles per gram wet weight) I, 310 ± 30; II, 540 ± 40; IV, 195 ± 60. D content was (picomoles per gram wet weight) I, 26 ± 6; II, 46 ± 13; IV, 33 ± 7. Surgical denervation 4–6 days previously reduced the norepinephrine content of layers I and II to 35 ± 10 (p < 0.001) and of IV to 60 ± 20 (p < 0.05) and the D content of layers I and II to 13 ± 6 and 6 ± 6 pmol/g, respectively (p < 0.01); D content of layer IV was unchanged. D production from 10−7 M 3,4-dihydroxyphenylalanine (DOPA) was (nanomoles per gram per minute) I, 0.2 ± 0.03; II, 0.7 ± 0.1; IV, 1.0 ± 0.04. DOPA consumption was (nanomoles per gram per minute) I, 0.6 ± 0.1; II, 1.4 ± 0.3; and IV, 1.8 ± 0.2. Denervation did not change D production or DOPA consumption. Glomeruli without arterioles or tubules, obtained by sieving, contained no D or NE and did not produce D from DOPA. We conclude that proximal tubules produced at least five times more D from DOPA than glomeruli and distal tubules. Renal nerves did not contribute significantly to D production. We found no evidence of specific D-containing nerves associated with rat glomeruli.


2000 ◽  
Vol 11 (3) ◽  
pp. 454-467
Author(s):  
GLENDA GOBÉ ◽  
XIAO-JU ZHANG ◽  
DESLEY A. WILLGOSS ◽  
ESTELLE SCHOCH ◽  
NICOLE A. HOGG ◽  
...  

Abstract. The promotion of cell survival and regeneration in acute renal failure (ARF) is important for restitution of renal function. This study analyzes the temporal and spatial relationship between expression of pro- and anti-apoptotic members of the Bcl-2 gene family (Bcl-2, Bcl-XL, Bax) and epidermal growth factor (EGF), insulin-like growth factor-1 (IGF-1), and transforming growth factor-β (TGF-β), growth factors that are thought to be reparative in ARF. A rat model of ischemic ARF involving 30 min of bilateral renal artery occlusion followed by reperfusion for 0 to 14 d was used. Apoptosis and mitosis were quantified and qualitative assessment was made of other cellular damage including necrosis and loss of cellular adhesion. Locality and level of expression of the Bcl-2 and growth factor proteins were determined using immunohistochemistry. Apoptosis peaked between 4 and 14 d postischemia in both proximal and distal tubules. Mitosis peaked at 2 d in proximal tubules and 4 to 14 in the distal tubules. A spatio-temporal relationship was observed between anti-apoptotic Bcl-2 gene family members and growth factors after ischemia-reperfusion. In control kidneys, expression of Bcl-2, Bcl-XL was low in epithelium of distal tubules, Bax had low-to-moderate expression in the proximal tubule and had low expression in the distal tubule, EGF and IGF-1 had low-to-moderate expression in the distal tubule, and TGF-β had low expression in the proximal tubule. In contrast, within 24 h of reperfusion, distal tubules showed a marked increase in expression of Bcl-2 and a moderate increase in Bcl-XL and Bax. Proximal tubules showed a marked increase in Bax expression and a moderate increase in Bcl-XL. Twenty-four hours after expression of the Bcl-2 proteins was increased, IGF-1 and EGF protein levels were increased in the distal tubule, similar to the Bcl-2 anti-apoptotic proteins, and were also detected in the adjacent proximal tubules, suggestive of paracrine action in these tubules. TGF-β expression was moderately increased in regenerating proximal tubules, but no relationship was seen with the pattern of expression of the Bcl-2 genes. An explanation of these results is that the distal tubule is adaptively resistant to ischemic injury via promotion of survival by anti-apoptotic Bcl-2 genes, and its survival allows expression of growth factors critical not only to the maintenance and regeneration of its own cell population (autocrine action), but also to the adjacent ischemia-sensitive proximal tubular cells (paracrine action).


1959 ◽  
Vol 37 (1) ◽  
pp. 113-117 ◽  
Author(s):  
T. F. Nicholson

When 20 U.S.P. units per kg of parathyroid extract were injected intravenously into dogs with unilateral distal tubular nephrosis, the phosphate excretion from the normal kidney increased significantly, but there was no change in the amount of phosphate excreted by the nephrotic kidney. In dogs with unilateral nephrosis affecting the first third or the last two thirds of the proximal tubules, parathyroid extract produced a similar increase in phosphate excretion by the normal and the nephrotic kidneys. It is concluded that the site of renal action of parathyroid extract is in the distal tubule and that its mode of action is to stimulate active excretion of phosphate.


1957 ◽  
Vol 35 (8) ◽  
pp. 641-644 ◽  
Author(s):  
T. F. Nicholson

The proximal tubules of the left kidney in dogs were damaged by the injection of 0.5% racemic sodium tartrate into the left renal artery. In other experiments the distal tubules were damaged by the injection of 0.05% mercuric chloride up the left ureter. In animals with proximal tubular damage, intravenous infusions of desoxycorticosterone or aldosterone which produced a significant drop in sodium excretion from the normal kidney had no effect on the amount of sodium excreted by the damaged kidney. In animals with distal tubular damage the effect of these hormones on the damaged kidney was as great as on the normal kidney.


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