Nephron heterogeneity of phosphate reabsorption: effect of parathyroid hormone

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.

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.


1984 ◽  
Vol 246 (1) ◽  
pp. F27-F31
Author(s):  
J. A. Haas ◽  
T. J. Berndt ◽  
A. Haramati ◽  
F. G. Knox

The administration of nicotinamide results in urinary phosphate excretions similar to those obtained with pharmacologic doses of parathyroid hormone (PTH). Free-flow micropuncture was performed to localize the nephron site(s) of inhibition of phosphate reabsorption by nicotinamide or PTH in thyroparathyroidectomized (TPTX) rats stabilized on a normal or low phosphate diet. In rats fed a normal phosphate diet phosphaturia was observed following either nicotinamide or PTH treatment. Nicotinamide inhibited phosphate reabsorption in the loop of Henle (pars recta) but not in the accessible proximal tubule. PTH inhibited phosphate reabsorption in both the accessible proximal tubule and the pars recta. In phosphate deprivation, the phosphaturic response to either nicotinamide or PTH was blunted. Although phosphate reabsorption was markedly inhibited in the accessible proximal tubule with both nicotinamide and PTH, subsequent reabsorption in the loop of Henle and distal tubule blunted the phosphaturia. We conclude that nicotinamide primarily inhibits phosphate reabsorption by the pars recta in rats fed a normal phosphate diet, whereas it inhibits phosphate reabsorption by the proximal convoluted tubule in rats fed a low phosphate diet. Furthermore, avid reabsorption of phosphate in the pars recta accounts for the resistance to the phosphaturic effect of nicotinamide or PTH seen in rats fed a low phosphate diet.


1985 ◽  
Vol 248 (5) ◽  
pp. F729-F733 ◽  
Author(s):  
A. Haramati

The present studies were performed to determine the capacity for phosphate reabsorption in superficial and deep nephron proximal tubules in vivo. Micropuncture experiments were performed in 20 acutely thyroparathyroidectomized (TPTX) Munich-Wistar rats fed a normal phosphate diet (0.7%). Four groups were infused with differing amounts of phosphate (0,2,4, or 6 mumol/min) to increase the filtered phosphate load. The sites selected for micropuncture were the superficial early distal tubule and the deep nephron loop of Henle, which reflect fractional phosphate delivery (FDPi%) from superficial and deep nephron proximal tubules, respectively. In response to phosphate infusions, plasma phosphate increased from 3.03 +/- 0.09 to 7.01 +/- 0.58 mM, and fractional phosphate excretion rose from 2 +/- 1 to 58 +/- 5%. FDPi% increased from both superficial (14 +/- 1 to 58 +/- 2%) and deep nephron proximal tubules (4 +/- 1 to 27 +/- 5%) but always remained lower from deep nephrons, reflecting more avid reabsorption by deep nephron proximal tubules. The maximal rate of phosphate reabsorption (max RPi/SNGFR) in the superficial proximal tubule was significantly less than in the deep nephron proximal tubule (3.2 +/- 0.4 vs. 5.1 +/- 0.1 pmol/nl). In seven of the phosphate-infused rats, parathyroid hormone (PTH, 33 U/kg bolus; 1 U X kg-1 X min-1) was added to the infusion following the initial collections. In the presence of PTH, the RPi/SNGFR was significantly lower in deep than in superficial proximal tubules (0.4 +/- 0.5 vs. 1.6 +/- 0.4 pmol/nl). Thus, the maximum capacity for phosphate reabsorption was greater in deep than in superficial nephrons in TPTX rats. Furthermore, in the presence of phosphate infusions, PTH inhibited phosphate reabsorption to a greater extent in deep than in superficial proximal tubules.


1983 ◽  
Vol 244 (2) ◽  
pp. F140-F149 ◽  
Author(s):  
E. Pastoriza-Munoz ◽  
D. R. Mishler ◽  
C. Lechene

The sites of enhanced phosphate (PO4) reabsorption after PO4 deprivation were investigated before and after infusion of parathyroid hormone (PTH) in acutely thyroparathyroidectomized rats. Animals were fed either a control PO4 diet (1.6% P) or a low PO4 diet (0.025% P) for 2 days or 7-10 days. In control rats, PTH decreased PO4 reabsorption in the proximal tubule, loop of Henle, and distal convolution. PO4 reabsorption in the proximal tubule was enhanced after 2 days of PO4 deprivation. In this group, proximal PO4 reabsorption was decreased by PTH but remained greater than in control rats (70 +/- 6 vs. 45 +/- 6 pmol/min; P less than 0.025). After PTH, PO4 reabsorption increased in the loop of Henle from 3 +/- 0.5 to 13 +/- 2 pmol/min (P less than 0.005), whereas it was unaltered in the distal convolution in PO4-deprived rats. PTH markedly increased fractional excretion of PO4 in control rats but not in PO4-deprived rats. After prolonged PO4 deprivation, PO4 reabsorption along the nephron was unaltered by PTH. These results demonstrate that acute PO4 deprivation enhances PO4 reabsorption in the proximal tubule, although the phosphaturic effect of PTH in this segment is not abolished. Resistance to the inhibitory effect of PTH on PO4 reabsorption in some portion of the loop of Henle and possibly also in the distal convolution accounts for the absence of a significant phosphaturic effect of the hormone in acutely PO4-deprived rats. Prolongation of PO4 deprivation results in unresponsiveness to PTH extending to the proximal tubule.


1978 ◽  
Vol 234 (4) ◽  
pp. F287-F290 ◽  
Author(s):  
J. A. Haas ◽  
T. Berndt ◽  
F. G. Knox

Previous micropuncture studies in rats have demonstrated that fractional phosphate delivery (FDP%) from superficial distal nephrons is higher than in urine. To determine whether this apparent reabsorption could be accounted for by a lower FDP% from the deep nephrons, FDP% was determined in free-low micropuncture from deep nephrons (DN) (ascending limb of the loop of Henle in the papilla), superficial nephrons (SN) (distal tubules in the cortex), and urine (duct of Bellini). In six acute thyroparathyroidectomized (TPTX) rats, FDP% in DN was significantly less than SN. The urinary fractional phosphate excretion (FEP%) was significantly less than in the SN, but not significantly different from the DN. In six chronic TPTX rats, FDP% in DN was significantly less than in SN. The urinary FEP% was significantly less than the FDP% in the SN, and significantly less than the FDP% in the DN, evidence which favors phosphate reabsorption in the terminal nephron. We conclude that in TPTX rats, which are conserving phosphate, deep nephrons reabsorb phosphate more avidly than superficial nephrons.


1990 ◽  
Vol 1 (2) ◽  
pp. 200-204
Author(s):  
A Rybczynska ◽  
A Hoppe ◽  
F G Knox

Phosphate deprivation causes a resistance to the phosphaturic effect of parathyroid hormone. The decreased phosphaturic response to parathyroid hormone in rats fed a low phosphate diet for 1 day can be restored by propranolol infusion. Free-flow micropuncture studies were performed to localize the nephron site of restoration of the phosphaturic effect of parathyroid hormone by propranolol in rats deprived of phosphate for one day. In animals fed low phosphate diet and in the presence of parathyroid hormone, propranolol infusion did not change phosphate delivery to the late proximal tubule; however, fractional delivery of phosphate to the early distal tubule was significantly increased from 18.3 +/- 2.9 to 32.2 +/- 4.1%. In rats fed a normal phosphate diet, propranolol infusion did not change phosphate delivery along the nephron. We conclude that the restoration of the phosphaturic effect of parathyroid hormone by propranolol infusion in rats deprived of phosphate for 1 day is primarily due to decreased reabsorption of phosphate by superficial loop segments, most likely the pars recta segment of the proximal tubule.


1981 ◽  
Vol 241 (6) ◽  
pp. F645-F648
Author(s):  
A. U. Sheth ◽  
H. O. Senekjian ◽  
H. Babino ◽  
T. F. Knight ◽  
E. J. Weinman

Free-flow micropuncture studies were performed in the Munich-Wistar rat to determine the nephron sites of gentamicin transport. The rats were infused with radiolabeled gentamicin and were volume-expanded with either isotonic sodium chloride or sodium bicarbonate. The fractional delivery of ultrafilterable gentamicin (FD) out of the superficial proximal tubule averaged 75% in both groups of animals. FD to the superficial distal tubule averaged 58.1 +/- 2.1% in saline-infused and 91.6 +/- 5.3% in bicarbonate-infused animals. FD to Henle's loop was 118.2 +/- 8.8 and 124.3 +/- 8.1% in saline- and bicarbonate-infused animals, respectively. FD to the base and tip of the papilla was not significantly different between the two groups and averaged 97.3 +/- 2.9 and 96.1 +/- 3.0% in the saline-infused and 100.5 +/- 2.6 and 94.3 +/- 2.8% in the bicarbonate-infused animals. FD to the base of the papilla was significantly lower than that to the loop of Henle in both groups. These studies indicate that gentamicin undergoes net reabsorption in juxtamedullary proximal tubules. Expansion of the extracellular fluid volume with saline or bicarbonate results in differing rates of gentamicin delivery to the superficial distal tubule but not to the base of the papilla. These findings suggest a significant degree of nephron heterogeneity for gentamicin transport in the rat kidney.


1979 ◽  
Vol 236 (4) ◽  
pp. F342-F348 ◽  
Author(s):  
C. A. Harris ◽  
M. A. Burnatowska ◽  
J. F. Seely ◽  
R. A. Sutton ◽  
G. A. Quamme ◽  
...  

Recollection micropuncture and clearance studies were carried out on thyroparathyroidectomized hamsters to clarify the localization of the effects of parathyroid hormone (PTH) on renal electrolyte transport. The clearance data confirmed that PTH inhibits phosphate and enhances calcium and magnesium reabsorption. These effects appeared to result from actions of the hormone in several parts of the nephron. In the proximal tubule PTH did not affect H2O reabsorption but inhibited phosphate reabsorption ((TF/P)PO4 increased from 0.46 +/- 0.04 to 0.57 +/- 0.03, P less than 0.02) and appeared to enhance calcium and magnesium reabsorption ((TF/UF)Ca decreased from 1.41 +/- 0.07 to 1.25 +/- 0.06, P less than 0.001, and (TF/UF)Mg from 1.66 +/- 0.10 to 1.51 +/- 0.08, P less than 0.05; in control animals (TF/UF)Ca increased from 1.51 +/- 0.10 to 1.65 +/- 0.11, P less than 0.01). PTH further inhibited phosphate reabsorption and enhanced calcium and magnesium reabsorption between the late proximal and early distal sites of puncture. Comparison of fractional deliveries of calcium and magnesium from the late distal tubule with their fractional excretions suggests an additional effect beyond the distal puncture site. The phosphaturic, but not the calcium- and magnesium-retaining, effects of PTH were abolished by a 16-h fast.


1985 ◽  
Vol 249 (6) ◽  
pp. F919-F922 ◽  
Author(s):  
T. J. Berndt ◽  
F. G. Knox

This study was performed to evaluate the nephron site(s) responsible for the blunted phosphaturic effect of parathyroid hormone during respiratory alkalosis. In normocapnic thyroparathyroidectomized rats, parathyroid hormone administration markedly increased the fractional excretion of phosphate (FEp) from 2.1 +/- 0.5 to 36.6 +/- 5.0%. However, in the respiratory alkalotic rats, parathyroid hormone administration did not significantly increase the FEp (1.4 +/- 0.9 to 5.9 +/- 2.2%). This blunted phosphaturic response to parathyroid hormone was not due to a blunted inhibition of phosphate reabsorption by the superficial proximal tubule, since parathyroid hormone administration significantly increased the fractional delivery of phosphate (FDp) at the superficial late proximal tubule in both normal (25.3 +/- 3.0 to 36.2 +/- 3.8%, delta 10.9 +/- 3.2%) and respiratory alkalotic rats (12.2 +/- 3.1 to 30.3 +/- 4.9%, delta 18.0 +/- 4.7%). Parathyroid hormone administration significantly increased the FDp at the superficial early distal tubule from 9.3 +/- 3.9 to 38.7 +/- 7.4% (delta 29.4 +/- 5.1%) in normal rats and from 4.5 +/- 1.7 to 12.9 +/- 3.4% (delta 8.5 +/- 3.2%) in the respiratory alkalotic rats. We conclude that the blunted phosphaturic response to parathyroid hormone in respiratory alkalotic rats is not due to a blunted inhibition of phosphate reabsorption by the proximal convoluted tubule but is primarily due to enhanced reabsorption by the pars recta segment of the proximal 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.


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