Nephron sites of action of nicotinamide on phosphate reabsorption

1984 ◽  
Vol 246 (1) ◽  
pp. F27-F31
Author(s):  
J. A. Haas ◽  
T. J. Berndt ◽  
A. Haramati ◽  
F. G. Knox
Keyword(s):  
Parathyroid Hormone ◽  
Proximal Tubule ◽  
Distal Tubule ◽  
Proximal Convoluted Tubule ◽  
Free Flow ◽  
Loop Of Henle ◽  
Phosphate Deprivation ◽  
Phosphate Reabsorption ◽  
Pars Recta ◽  
Sites Of Action

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.

scholarly journals Effect of propranolol on phosphate reabsorption by superficial nephron segments in response to parathyroid hormone in phosphate-deprived rats.

1990 ◽  
Vol 1 (2) ◽  
pp. 200-204
Author(s):  
A Rybczynska ◽  
A Hoppe ◽  
F G Knox
Keyword(s):  
Parathyroid Hormone ◽  
Proximal Tubule ◽  
Distal Tubule ◽  
Free Flow ◽  
Phosphate Deprivation ◽  
Phosphate Reabsorption ◽  
Nephron Segments ◽  
Pars Recta

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.

Nephron site of resistance to phosphaturic effect of PTH during respiratory alkalosis

1985 ◽  
Vol 249 (6) ◽  
pp. F919-F922 ◽  
Author(s):  
T. J. Berndt ◽  
F. G. Knox
Keyword(s):  
Parathyroid Hormone ◽  
Proximal Tubule ◽  
Distal Tubule ◽  
Fractional Excretion ◽  
Respiratory Alkalosis ◽  
Proximal Convoluted Tubule ◽  
Phosphate Reabsorption ◽  
Hormone Administration ◽  
Pars Recta ◽  
Fractional Excretion Of Phosphate

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.

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
Keyword(s):  
Parathyroid Hormone ◽  
Proximal Tubule ◽  
Distal Tubule ◽  
Proximal Tubules ◽  
Loop Of Henle ◽  
Phosphate Reabsorption ◽  
Phosphate Excretion ◽  
Before And After ◽  
Superficial And Deep Nephrons ◽  
Nephron Heterogeneity

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.

Effect of phosphate deprivation on phosphate reabsorption in rat nephron: role of PTH

1983 ◽  
Vol 244 (2) ◽  
pp. F140-F149 ◽  
Author(s):  
E. Pastoriza-Munoz ◽  
D. R. Mishler ◽  
C. Lechene
Keyword(s):  
Parathyroid Hormone ◽  
Proximal Tubule ◽  
Fractional Excretion ◽  
Inhibitory Effect ◽  
Loop Of Henle ◽  
Phosphate Deprivation ◽  
Phosphate Reabsorption ◽  
Before And After ◽  
Distal Convolution

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.

Response to parathyroid hormone in defined segments of proximal tubule

1976 ◽  
Vol 230 (2) ◽  
pp. 286-290 ◽  
Author(s):  
RJ Hamburger ◽  
NL Lawson ◽  
JH Schwartz
Keyword(s):  
Parathyroid Hormone ◽  
Proximal Tubule ◽  
Proximal Convoluted Tubule ◽  
Base Line ◽  
Fluid Absorption ◽  
Functional Heterogeneity ◽  
Intrinsic Absorption ◽  
Pars Recta ◽  
Intrinsic Capacity ◽  
Control Fluid

Previous investigations have suggested that there is a functional heterogeneity along the length of the proximal convoluted tubule. This study was designed to confirm and extend these suggestions by examining the intrinsic absorption of fluid and the effect of parathyroid hormone (PTH) on net fluid absorption in isolated, anatomically defined segments of rabbit superficial proximal tubules. The EPCT (early proximal convoluted tubule), LPCT (late proximal convoluted tubule), and PR (pars recta) segments were studied under controlled conditions by the isolated perfused tubule technique. In 23 EPCT, base-line fluid absorption was 1.38 +/- 0.04 (SE), a rate significantly higher than those of 11 LPCT (0.62 +/- 0.02; P less than 0.001) and 12 PR (0.52 +/- 0.03 nl mm-1 min-1, P less than 0.001) segments. In 10 EPCT, mean control fluid absorption was 1.31 +/- 0.04 nl mm-1 min-1; addition of PTH resulted in a decrease to 0.95 +/- 0.05 nl mm-1 min-1 (P less than 0.001); and, after removal of PTH, fluid absorption increased (P less than 0.001). Parathyroid hormone had no effect on either seven LPCT segments or six PR segments. These results demonstrate differences in intrinsic capacity to absorb fluid by anatomically defined segments of the rabbit proximal tubule. This functional heterogeneity is further supported by the observed differential response to PTH by the various anatomic segments of the proximal tubule.

Proximal tubule site of inhibition of phosphate reabsorption by calcitonin

1984 ◽  
Vol 246 (6) ◽  
pp. F927-F930 ◽  
Author(s):  
T. J. Berndt ◽  
F. G. Knox
Keyword(s):  
Proximal Tubule ◽  
Salmon Calcitonin ◽  
Distal Tubule ◽  
Proximal Convoluted Tubule ◽  
Phosphate Reabsorption

The present study was performed to evaluate the nephron site of inhibition by calcitonin of phosphate reabsorption in the thyroparathyroidectomized rat. Pharmacologic doses of salmon calcitonin markedly inhibited fluid and phosphate reabsorption by the superficial proximal tubule. However, continued phosphate reabsorption between the superficial late proximal and early distal tubule, as well as along the distal tubule, blunted the phosphaturic effect of calcitonin. We conclude that the phosphaturic effect of a pharmacologic dose of salmon calcitonin is primarily due to an inhibition of fluid and phosphate reabsorption by the proximal convoluted tubule.

Effect of cAMP analogue infusion on phosphate reabsorption in phosphate-deprived rats

1988 ◽  
Vol 255 (1) ◽  
pp. F96-F99
Author(s):  
T. J. Berndt ◽  
M. J. Onsgard ◽  
F. G. Knox
Keyword(s):  
Parathyroid Hormone ◽  
Proximal Convoluted Tubule ◽  
Straight Tubule ◽  
Cyclic Monophosphate ◽  
Phosphate Reabsorption ◽  
Phosphate Excretion ◽  
Camp Analogue ◽  
Proximal Straight Tubule ◽  
Pars Recta ◽  
Distal Tubules

The present study was performed to compare the effects of 8-(4-chlorophenylthio)-adenosine 3',5'-cyclic monophosphate (cAMP analogue) and parathyroid hormone (PTH) infusion on segmental phosphate reabsorption in phosphate-deprived rats. Micropunctures of the late proximal and the early distal tubules were performed in acutely thyroparathyroidectomized (TPTX) rats fed either a normal (NPD) or low phosphate diet (LPD), and the phosphaturic response to infusion of PTH and cAMP analogue was evaluated. In NPD rats, PTH (n = 10) and the cAMP analogues (n = 11) markedly increased urinary phosphate excretion, due to inhibition of phosphate reabsorption along the proximal convoluted tubule and pars recta. In phosphate-deprived rats, PTH (n = 10) or the cAMP analogue (n = 11) did not increase urinary phosphate excretion. However, PTH and the cAMP analogue inhibited phosphate reabsorption along the proximal convoluted tubule but not in the pars recta in phosphate-deprived rats. We conclude that cAMP analogue infusion mimics the effect of PTH infusion on phosphate reabsorption along the proximal convoluted and proximal straight tubule in normal and phosphate-deprived rats. The resistance to the phosphaturic effect of PTH and cAMP infusions is a result of a blunted inhibition of phosphate reabsorption by the proximal convoluted tubule and also an increased phosphate reabsorption by the proximal straight tubule.

Effects of parathyroid hormone on electrolyte transport in the hamster nephron

1979 ◽  
Vol 236 (4) ◽  
pp. F342-F348 ◽  
Author(s):  
C. A. Harris ◽  
M. A. Burnatowska ◽  
J. F. Seely ◽  
R. A. Sutton ◽  
G. A. Quamme ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Proximal Tubule ◽  
Distal Tubule ◽  
Electrolyte Transport ◽  
Puncture Site ◽  
Phosphate Reabsorption ◽  
Renal Electrolyte Transport ◽  
Clearance Studies ◽  
Calcium And Magnesium

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.

Reabsorption and secretion of alpha-ketoglutarate along the rat nephron: a micropuncture study

1985 ◽  
Vol 248 (3) ◽  
pp. F404-F412 ◽  
Author(s):  
B. Ferrier ◽  
M. Martin ◽  
G. Baverel
Keyword(s):  
Proximal Tubule ◽  
Progressive Increase ◽  
Proximal Convoluted Tubule ◽  
Loop Of Henle ◽  
Progressive Reduction ◽  
Acid Base ◽  
Luminal Membrane ◽  
Pars Recta ◽  
Micropuncture Study ◽  
Steady State Levels

The transport of alpha-ketoglutarate (alpha-KG) across the luminal membrane of the rat nephron was studied by micropuncture and microassay techniques. In normal and acidotic rats, approximately 75% of the filtered alpha-KG was reabsorbed in the proximal tubule and 20% in the pars recta and/or loop of Henle at endogenous plasma concentration of alpha-KG. A progressive elevation to steady-state levels of plasma alpha-KG resulted in a progressive reduction of the fractional reabsorption of alpha-KG in the proximal tubule as well as in a progressive increase in the fractional reabsorption of alpha-KG in the pars recta and/or loop of Henle. At plasma alpha-KG concentration 20-40 times above normal, reabsorption of alpha-KG was found to be limited by a maximal tubular capacity. In alkalotic rats, net secretion of alpha-KG in the early proximal convoluted tubule, net reabsorption in the remainder of the proximal convoluted tubule, and net secretion in the pars recta and/or loop of Henle were observed. These micropuncture data indicate that, depending on the acid-base conditions, net reabsorption or net secretion of alpha-KG may occur in at least two distinct sites along the rat nephron.

Adaptation of deep and superficial nephrons to changes in dietary phosphate intake

1983 ◽  
Vol 244 (3) ◽  
pp. F265-F269 ◽  
Author(s):  
A. Haramati ◽  
J. A. Haas ◽  
F. G. Knox
Keyword(s):  
Proximal Tubule ◽  
Distal Tubule ◽  
Proximal Tubules ◽  
Loop Of Henle ◽  
Phosphate Reabsorption ◽  
Phosphate Intake ◽  
Phosphate Excretion ◽  
Dietary Phosphate ◽  
Renal Phosphate Excretion ◽  
High Phosphate

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.

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