Possible Relationship of Gluconeogenesis to Modulation of Phosphate Transport in the Proximal Tubule

1982 ◽  
pp. 55-64
Author(s):  
Thomas P. Dousa
Keyword(s):  
Proximal Tubule ◽  
Phosphate Transport ◽  
Relationship Of

Stimulation of phosphate transport in the proximal tubule by metabolic substrates

1984 ◽  
Vol 247 (4) ◽  
pp. F582-F587 ◽  
Author(s):  
S. R. Gullans ◽  
P. C. Brazy ◽  
L. J. Mandel ◽  
V. W. Dennis
Keyword(s):  
Proximal Tubule ◽  
Fluid Transport ◽  
Initial Rate ◽  
Tricarboxylic Acid Cycle ◽  
Phosphate Transport ◽  
Glucose Absorption ◽  
Metabolic Substrates ◽  
Tricarboxylic Acid Cycle Intermediates ◽  
Stimulation Of

Studies of phosphate transport in the proximal tubule have recently focused on interactions with cellular metabolism. The present studies demonstrate that two fatty acids, valerate and butyrate, and two tricarboxylic acid cycle intermediates, succinate and malate, stimulate net phosphate transport in the rabbit proximal tubule by 34-117%. Valerate had no effect on the total uptake of inorganic [32P]phosphate into suspensions of proximal tubules but did enhance the initial rate of influx. Net fluid transport was unaffected by these substrates although glucose absorption increased by 10-15% following the addition of either valerate or succinate. Since valerate, butyrate, and succinate are known to stimulate gluconeogenesis and respiration, we evaluated the role of gluconeogenesis in the stimulation of phosphate transport. The addition of 3-mercaptopicolinate (1 mM), an inhibitor of gluconeogenesis, did not alter phosphate transport, nor did it prevent the valerate-induced stimulation of phosphate transport. We conclude that valerate, butyrate, succinate, and malate enhance phosphate transport by the proximal convoluted tubule. This action appears to be unrelated to effects on gluconeogenesis and may be related to close links between phosphate transport and oxidative metabolism.

scholarly journals Signaling pathways utilized by PTH and dopamine to inhibit phosphate transport in mouse renal proximal tubule cells

2009 ◽  
Vol 296 (2) ◽  
pp. F355-F361 ◽  
Author(s):  
Rochelle Cunningham ◽  
Rajatsubhra Biswas ◽  
Marc Brazie ◽  
Deborah Steplock ◽  
Shirish Shenolikar ◽  
...  
Keyword(s):  
Proximal Tubule ◽  
Signaling Pathways ◽  
Phosphate Transport ◽  
Inhibitory Effect ◽  
Renal Proximal Tubule ◽  
Proximal Tubule Cells ◽  
Phosphate Cotransport ◽  
Tubule Cells ◽  
Renal Proximal Tubule Cells ◽  
Sodium Phosphate Cotransport

The present experiments were designed to detail factors regulating phosphate transport in cultured mouse proximal tubule cells by determining the response to parathyroid hormone (PTH), dopamine, and second messenger agonists and inhibitors. Both PTH and dopamine inhibited phosphate transport by over 30%. The inhibitory effect of PTH was completely abolished in the presence of chelerythrine, a PKC inhibitor, but not by Rp-cAMP, a PKA inhibitor. By contrast, both chelerythrine and Rp-cAMP blocked the inhibitory effect of dopamine. Chelerythrine inhibited PTH-mediated cAMP accumulation but also blocked the inhibitory effect of 8-bromo-cAMP on phosphate transport. On the other hand, Rp-cAMP had no effect on the ability of DOG, a PKC activator, to inhibit phosphate transport. PD98059, an inhibitor of MAPK, had no effect on PTH- or dopamine-mediated inhibition of sodium-phosphate cotransport. Finally, compared with 8-bromo-cAMP, 8-pCPT-2′- O-Me-cAMP, an activator of EPAC, had no effect on phosphate transport. These results outline significant differences in the signaling pathways utilized by PTH and dopamine to inhibit renal phosphate transport. Our results also suggest that activation of MAPK is not critically involved in PTH- or dopamine-mediated inhibition of phosphate transport in mouse renal proximal tubule cells in culture.

Nucleotide inhibition of phosphate transport in the renal proximal tubule

1983 ◽  
Vol 245 (2) ◽  
pp. F263-F271
Author(s):  
R. P. Lang ◽  
N. Yanagawa ◽  
E. P. Nord ◽  
L. Sakhrani ◽  
S. H. Lee ◽  
...  
Keyword(s):  
Proximal Tubule ◽  
Competitive Inhibition ◽  
Specific Activity ◽  
Direct Action ◽  
Dilution Effect ◽  
Phosphate Transport ◽  
Inhibitory Effect ◽  
P Uptake ◽  
Luminal Membrane ◽  
P Flux

The observation that NAD inhibits sodium-dependent phosphate (P) uptake by the luminal brush border membrane (BBM) of the proximal tubule prompted us to examine the specificity and mechanism of this process. Addition of 10(-5) M NAD to the perfusate of isolated perfused rabbit proximal straight tubules inhibited lumen-to-bath P flux by approximately 50%. ADP-ribose had an identical effect, whereas nicotinamide had no effect. ADP and 5'-AMP (10(-5) M) also inhibited P flux. Na-dependent uptake of 32P by rabbit BBM vesicles was inhibited by 0.1-0.3 mM NAD, ADP-ribose, ADP, ATP, 5'-AMP, and GDP, which were preincubated with the vesicles for 30 min. The kinetics of inhibition showed an apparent increase in the Km for P but no change in Vmax. These findings are consistent with "competitive inhibition." The nucleotides inhibited P uptake even when BBM alkaline phosphatase was inhibited by 96% with 10 mM theophylline. Evidence of nonspecific phosphatase activity was present, since incubation of BBM with 0.1 mM solution of nucleotides for 30 min resulted in an elevation of free P in the medium of approximately 0.15-0.22 mM. Correction of 32P specific activity for this change resulted in values for Km and Vmax that were not significantly different from control. The "competitive inhibition" could thus be ascribed to an isotope-dilution effect. There was no evidence to suggest that NAD caused ADP-ribosylation of the luminal membrane. These studies indicate that adenine and guanine nucleotides do not inhibit P transport by a direct action on the luminal membrane of the proximal tubule but do inhibit lumen-to-bath P flux in isolated perfused proximal tubules at concentrations of 10(-5) M. Since there is no direct inhibitory effect of these compounds at the level of the BBM, it is possible that they inhibit P transport by altering some event subsequent to the transfer of P across the luminal membrane.

Presence of multiple sodium-dependent phosphate transport processes in proximal brush-border membrane

1987 ◽  
Vol 252 (2) ◽  
pp. F226-F231 ◽  
Author(s):  
J. J. Walker ◽  
T. S. Yan ◽  
G. A. Quamme
Keyword(s):  
Proximal Tubule ◽  
Brush Border ◽  
Brush Border Membrane ◽  
Phosphate Transport ◽  
Transport Processes ◽  
Proximal Tubules ◽  
High Affinity ◽  
Medullary Tissue ◽  
Sodium Dependent ◽  
Early Proximal Tubule

Renal brush-border membrane phosphate transport was studied in early and late segments of the pig proximal tubule. Vesicles were prepared from early proximal tubules (outer cortical tissue) and late proximal tubules (outer medullary tissue). Sodium-dependent phosphate uptake into brush-border membrane vesicles was determined using voltage clamp at 5-6 s, 21 degrees C. Sodium-dependent D-glucose uptake was determined to verify the cortical and medullary tissue cuts. At pH 8.0 (pHi = pHo), two sodium-dependent phosphate transport systems were evident in the early proximal tubule: a high-affinity system [Km, 0.06 +/- 0.01 mM; maximal transport activity (Vmax), 3.6 +/- 1.1 nmol X mg protein-1 X min-1] and a low-affinity system (Km, 4.11 +/- 0.02 mM; Vmax, 9.7 +/- 0.7 nmol X mg protein-1 X min-1). In the late proximal tubule at pH 8.0, only a single high-affinity transport process (Km, 0.19 +/- 0.7 mM; Vmax, 3.4 +/- 0.5 nmol X mg protein-1 X min-1) was evident. D-Glucose kinetics at pH 7.0 revealed both a high-affinity (Km, 0.55 +/- 0.09 mM) and a low-affinity (Km, 20.09 +/- 1.39 mM) system in the early proximal segment and a single high-affinity (Km, 1.27 +/- 0.36 mM) process in the late segment. These data suggest that two systems, distinct in their affinities and capacities, are involved in both D-glucose and phosphate transport across the brush-border membrane of the early proximal tubule, but that only a single high-affinity system is present in the late segment.

Effects of Intraluminal sulfate on electrolyte transfers along the perfused rat nephron

1981 ◽  
Vol 59 (2) ◽  
pp. 122-130 ◽  
Author(s):  
Gary A. Quamme
Keyword(s):  
Proximal Tubule ◽  
Chloride Transport ◽  
Distal Tubule ◽  
Phosphate Transport ◽  
Loop Of Henle ◽  
Magnesium Transport ◽  
Calcium And Magnesium ◽  
A Site ◽  
Distal Delivery

Superficial nephrons were perfused in vivo to determine the effect of intraluminal sulfate (1–20 mM) on electrolyte reabsorption in the rat with special reference to calcium and magnesium transport. This technique allowed us the opportunity of investigating separate electrolyte transfers without alteration of extrarenal influences. The major amount of perfused sulfate was absorbed in the proximal tubule with little absorption distal to the late proximal collection site. Phosphate transport was not affected by high luminal sulfate concentrations indicating distinct reabsorptive mechanisms for these two anions. Intraluminal sulfate significantly inhibited calcium and magnesium reabsorption in the proximal tubule, loop of Henle, and superficial distal tubule, in distinction to modest effects on sodium transport in these nephron segments. Chloride transport was not altered. The inhibition of divalent cation transfer was not quantitively similar in the different tubule segments. Small amounts of sulfate completely inhibited proximal calcium and magnesium reabsorption with little effect on transport within the loop of Henle. Enhanced distal delivery of sulfate significantly inhibited calcium and magnesium reabsorption in the distal tubule, a site where the sulfate anion is not reabsorbed. These results demonstrate the importance of distal delivery of anionic ligands capable of forming nonreabsorbable complexes. Thus distal calcium and magnesium transport may be greatly modified by proximal control of anion reabsorption.

Effect of Phlorhizin on Renal Glucose and Phosphate Transport in the Dog

1979 ◽  
Vol 57 (4) ◽  
pp. 367-374 ◽  
Author(s):  
Sung-Feng Wen
Keyword(s):  
Proximal Tubule ◽  
Sodium Transport ◽  
Fractional Excretion ◽  
Phosphate Transport ◽  
Reciprocal Relationship ◽  
Sodium Reabsorption ◽  
Group I ◽  
Glucose Reabsorption ◽  
Fractional Excretion Of Sodium ◽  
Proximal Tubular

1. Clearance and micropuncture studies were performed in 19 thyroparathyroidectomized dogs to examine the inter-relationship between the renal transport of sodium, glucose and phosphate. 2. All experiments were carried out before and after the intravenous administration of phlorhizin [7 mg (15 μmol)/kg] with a sustaining infusion of the same dose/h. Thirteen dogs were studied during hydropenia (group I) and six dogs in the volume-expanded state (group II). 3. In the proximal tubule, phlorhizin significantly reduced sodium reabsorption in hydropenic dogs, but had no effect in volume-expanded dogs. Proximal tubular glucose reabsorption was completely inhibited by phlorhizin in both groups, but no significant change in phosphate reabsorption was observed. 4. Fractional glucose excretion in the urine reached 83–89% after phlorhizin, values significantly less than 100%, suggesting a residual reabsorption of glucose in a more distal segment or in deep nephrons. The changes in fractional excretion of sodium and phosphate were significantly correlated. 5. The effect of phlorhizin on both sodium and glucose reabsorption in the proximal tubule in hydropenic dogs suggests the existence of a co-transport mechanism, whereas the absence of an effect on sodium transport in volume-expanded dogs despite complete inhibition of glucose reabsorption indicates the existence of a sodium-independent component of net proximal tubular glucose transport. 6. Absence of the effect of phlorhizin on proximal tubular phosphate transport in the face of a significant reduction in sodium reabsorption implies that the reciprocal relationship between glucose and phosphate transport could be masked by the changes in sodium transport. Thus the sodium-phosphate transport relationship may prevail over that of glucose-phosphate in the proximal tubule.

scholarly journals Novel developments in differentiating the role of renal and intestinal sodium hydrogen exchanger 3

2016 ◽  
Vol 311 (6) ◽  
pp. R1186-R1191 ◽  
Author(s):  
Jessica A. Dominguez Rieg ◽  
Samantha de la Mora Chavez ◽  
Timo Rieg
Keyword(s):  
Proximal Tubule ◽  
Knockout Mice ◽  
Collecting Duct ◽  
Phosphate Transport ◽  
Thick Ascending Limb ◽  
Sodium Hydrogen Exchanger ◽  
Novel Drug ◽  
Therapeutic Considerations ◽  
Insight Into

The Na+/H+ exchanger isoform 3 (NHE3) facilitates Na+ absorption and H+ secretion and is expressed in the intestine, proximal tubule, and thick ascending limb of the kidney. While the function of NHE3 for Na+ and [Formula: see text](re)absorption has been defined using conventional NHE3 knockout mice (NHE3−/−), the recent generation of conditional NHE3 knockout mice started to give critical new insight into the role of this protein by allowing for temporal and spatial control of NHE3 expression. For example, in contrast to NHE3−/− mice, knockout of NHE3 in the S1 and S2 segments of the proximal tubule or along the entire tubule/collecting duct does not cause any lethality. Nonabsorbable NHE3 inhibitors have been developed, and preclinical as well as clinical trials indicate possible pharmacological use in fluid overload, hypertension, chronic kidney disease, hyperphosphatemia, and constipation. Some of the therapeutic considerations seem to be directly related to the pharmacodynamic properties of these drugs; however, little is known about the effects of these nonabsorbable NHE3 inhibitors on intestinal phosphate transport and the mechanisms so far remain elusive. This review focuses on novel findings of NHE3 in the intestine and the kidney as well as novel drug developments targeting NHE3.

Distal site of action of parathyroid hormone on phosphate reabsorption

1975 ◽  
Vol 229 (6) ◽  
pp. 1556-1560 ◽  
Author(s):  
FG Knox ◽  
C Lechene
Keyword(s):  
Parathyroid Hormone ◽  
Proximal Tubule ◽  
Phosphate Transport ◽  
Distal Nephron ◽  
Phosphate Reabsorption ◽  
Site Of Action ◽  
Flow Experiments ◽  
Filtered Load ◽  
Stop Flow ◽  
Distal Site

The sites of inhibited phosphate transport following administration of bovine parathyroid hormone (bPTH) to thyroparathyroidectomized (TPTX) dogs were investigated. Phosphate reabsorption by the proximal and distal nephron was studied using recollection micropuncture, stop-flow methodology, and electron-probe microanalysis. Following bPTH, delivery of phosphate from the proximal tubule increased from 26 to 37% of the filtered load, P less than .01. Fractional phosphate excretion increased from 2.3 +/- 1.5 to 21.4 +/- 2.3%, P less than .001. The increased delivery of phosphate at the point of micropuncture in the proximal tubule accounted for approximately half of the phosphaturia. In six TPTX dogs, which were saline loaded, similiar increases in phosphate delivery from the proximal tubule from 27 +/- 1 to 36 +/- 2% of the filtered load resulted in a strikingly smaller phosphaturia, 5.1 +/- 1 to 9.8 +/- 2.4%, NS. In stop-flow experiments, phosphate concentratin ratios were slightly increased in the proximal nephron and markedly increased in the distal nephron following bPTH. It is concluded that parathyroid hormone markedly decreases phosphate transport in the distal nephron.

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