scholarly journals Maturation of rat proximal tubule chloride permeability

2005 ◽  
Vol 289 (6) ◽  
pp. R1659-R1664 ◽  
Author(s):  
Michel Baum ◽  
Raymond Quigley

We have previously shown that neonate rabbit tubules have a lower chloride permeability but comparable mannitol permeability compared with adult proximal tubules. The surprising finding of lower chloride permeability in neonate proximals compared with adults impacts net chloride transport in this segment, which reabsorbs 60% of the filtered chloride in adults. However, this maturational difference in chloride permeability may not be applicable to other species. The present in vitro microperfusion study directly examined the chloride and mannitol permeability using in vitro perfused rat proximal tubules during postnatal maturation. Whereas there was no maturational change in mannitol permeability, chloride permeability was 6.3 ± 1.3 × 10−5 cm/s in neonate rat proximal convoluted tubule and 16.1 ± 2.3 × 10−5 cm/s in adult rat proximal convoluted tubule ( P < 0.01). There was also a maturational increase in chloride permeability in the rat proximal straight tubule (5.1 ± 0.6 × 10−5 cm/s vs. 9.3 ± 0.6 × 10−5 cm/s, P < 0.01). There was no maturational change in bicarbonate-to-chloride permeabilities ( PHCO3/ PCl) in the rat proximal straight tubules (PST) and proximal convoluted tubules (PCT) or in the sodium-to-chloride permeability ( PNa/ PCl) in the proximal straight tubule; however, there was a significant maturational decrease in proximal convoluted tubule PNa/ PCl with postnatal development (1.31 ± 0.12 in neonates vs. 0.75 ± 0.06 in adults, P < 0.001). There was no difference in the transepithelial resistance measured by current injection and cable analysis in the PCT, but there was a maturational decrease in the PST (7.2 ± 0.8 vs. 4.6 ± 0.1 Ω·cm2, P < 0.05). These studies demonstrate there are maturational changes in the rat paracellular pathway that impact net NaCl transport during development.

2002 ◽  
Vol 283 (3) ◽  
pp. F525-F531 ◽  
Author(s):  
Raymond Quigley ◽  
Michel Baum

The early proximal tubule preferentially reabsorbs organic solutes and bicarbonate over chloride ions, resulting in a luminal fluid with a higher chloride concentration than that in blood. From this late proximal tubular fluid, one-half of NaCl reabsorption by the adult proximal tubule is active and transcellular and one-half is passive and paracellular. The purpose of the present in vitro microperfusion study was to determine the characteristics of passive chloride transport and permeability properties of the adult and neonatal proximal straight tubules (PST). In tubules perfused with a late proximal tubular fluid, net passive chloride flux was 131.7 ± 37.7 pmol · mm−1 · min−1in adult tubules and −17.1 ± 23.3 pmol · mm−1 · min−1 in neonatal proximal tubules ( P < 0.01). Chloride permeability was 10.94 ± 5.21 × 10−5 cm/s in adult proximal tubules and −1.26 ± 1.84 × 10−5 cm/s in neonatal proximal tubules ( P< 0.05). Thus neonatal PST have a chloride permeability not different from zero and have no net passive chloride transport. Bicarbonate permeability is also less in neonates than adults in this segment (−0.07 ± 0.03 × 10−5 vs. 0.93 ± 0.27 × 10−5 cm/s, P < 0.01). Neonatal PST have higher sodium-to chloride and bicarbonate-to-chloride permeability ratios than adult PST. However, mannitol and sucrose permeabilities were not different in adult proximal tubules and neonatal PST. Transepithelial resistance was measured using current injection and cable analysis. The resistance was 6.7 ± 0.7 Ω · cm2 in adult tubules and 11.3 ± 1.4 Ω · cm2 in neonatal PST ( P < 0.01). In conclusion, there are significant maturational changes in the characteristics of the PST paracellular pathway affecting transport in this nephron segment.


1998 ◽  
Vol 274 (5) ◽  
pp. F883-F888 ◽  
Author(s):  
Mehul Shah ◽  
Raymond Quigley ◽  
Michel Baum

The present in vitro microperfusion study compared the mechanism and rates of NaCl transport in neonatal and adult rabbit proximal straight tubules. In proximal straight tubules perfused with a late proximal tubular fluid and bathed in a serumlike albumin solution, the rate of volume absorption ( J V) was 0.54 ± 0.10 and 0.12 ± 0.05 nl ⋅ mm−1 ⋅ min−1in adults and neonates, respectively ( P < 0.05). With the addition of 10−5 M bath ouabain, J Vdecreased to 0.27 ± 0.07 and −0.03 ± 0.04 nl ⋅ mm−1 ⋅ min−1in adult and neonatal tubules, respectively ( P < 0.05), consistent with lower rates of active and passive NaCl transport in the neonatal proximal straight tubule. The effect of luminal sodium and chloride removal on intracellular pH was used to assess the relative rates of Na+/H+and Cl−/base exchange. The rates of Na+/H+and Cl−/base exchange were approximately fivefold less in neonatal proximal straight tubules than adult tubules. In both neonatal and adult proximal straight tubules, the rate of Cl−/base exchange was not affected by formate, bicarbonate, or cyanide and acetazolamide, consistent with Cl−/OH−exchange. These data demonstrate an increase in proximal straight tubule NaCl transport during postnatal renal development.


1988 ◽  
Vol 255 (1) ◽  
pp. F96-F99
Author(s):  
T. J. Berndt ◽  
M. J. Onsgard ◽  
F. G. Knox

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.


1985 ◽  
Vol 249 (5) ◽  
pp. F704-F712
Author(s):  
U. Kragh-Hansen ◽  
H. Roigaard-Petersen ◽  
M. I. Sheikh

The activity of the Na+-H+ exchanger in rabbit proximal tubule was investigated by using luminal membrane vesicles prepared from "outer cortex" (proximal convoluted tubule) or "outer medulla" (proximal straight tubule). The purity of the preparations was examined by measuring the activity of several marker enzymes, and the degree of cross-contamination and the functional state of the membrane vesicles were assessed by studying Na+-dependent uptake of D-glucose. The Na+ uptake by pars convoluta membrane vesicles exhibited an overshoot in the presence of an intravesicular greater than extravesicular H+ gradient. The overshoot was eliminated by omitting or reversing the transmembranal H+ gradient or by adding amiloride. In contrast, Na+ uptake by pars recta membrane vesicles did not show an overshoot and was independent of H+ gradients and of amiloride. However, Na+ uptake by pars recta membrane vesicles pretreated with monensin exhibited an overshoot. This overshoot apparently was amiloride insensitive. The findings propose that the Na+-H+ exchanger is predominantly operative in the proximal convoluted tubule and is either lacking or of minor significance in the proximal straight tubule.


1977 ◽  
Vol 232 (1) ◽  
pp. F20-F25 ◽  
Author(s):  
D. G. Warnock ◽  
M. B. Burg

Proximal straight tubules from rabbit kidneys were perfused in vitro in order to study transport of bicarbonate. Total CO2 content was measured in perfused and collected tubule fluid, using microcalorimetry. When the initial perfusate and bath contained 25 mM bicarbonate, the concentration of total CO2 decreased in the collected tubule fluid, indicating net reabsorption of bicarbonate. When the initial perfusate contained no bicarbonate and the bath contained 25 mM bicarbonate, total CO2 appeared in the collected tubule fluid. The rate at which total CO2 appeared in the tubule fluid was rapid, indicating a high permeability. Proximal straight tubules from superficial and juxtamedullary nephrons were compared and found to differ in permeability to CO2 and in transport rate. This functional heterogeneity may affect urinary acidification when there is redistribution of renal blood flow.


2000 ◽  
Vol 278 (4) ◽  
pp. F596-F602 ◽  
Author(s):  
Mehul Shah ◽  
Raymond Quigley ◽  
Michel Baum

We have recently demonstrated that the rates of both active and passive proximal straight tubule (PST) NaCl transport in neonatal rabbits were less than in adults. In this segment NaCl entry across the apical membrane is via parallel Na+/H+ and Cl−/OH− exchangers, which increases in activity with maturation. The present in vitro microperfusion study examined whether thyroid hormone plays a role in the maturational increase in PST NaCl transport. Neonatal and adult PST were perfused with a high-chloride-low bicarbonate solution without organic solutes, simulating late proximal tubule fluid. Thyroid hormone-treated neonates had a higher rate of PST total and passive NaCl transport. In 8-wk-old animals that were hypothyroid since birth, the maturational increase in total and passive NaCl transport was prevented. Thyroid treatment for 4 days in hypothyroid 8-wk-old rabbits increased the rate of both total and passive NaCl transport. The maturational increases in both Na+/H+ and Cl−/OH− exchange activities were blunted in 8-wk-old hypothyroid animals and increased to control levels with thyroid treatment. This study demonstrates that thyroid hormone is a factor responsible for the maturational increase in both active and passive PST NaCl transport.


1992 ◽  
Vol 83 (3) ◽  
pp. 307-311 ◽  
Author(s):  
Pnina Scherzer ◽  
Hanna Wald ◽  
Dvora Rubinger ◽  
Mordecai M. Popovtzer

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.


2004 ◽  
Vol 286 (3) ◽  
pp. F477-F482 ◽  
Author(s):  
Michel Baum ◽  
Raymond Quigley

Proximal straight tubules (PST) from both neonatal and hypothyroid adult rabbits have a lower rate of passive volume absorption when perfused with a high-chloride solution simulating late proximal tubular fluid than adult rabbit PST. We hypothesized that the maturational increase in serum thyroid hormone levels mediates the developmental changes in PST paracellular permeability. Neonatal tubules had lower chloride permeability, higher transepithelial resistance, but comparable mannitol permeability compared with adult PST. The present in vitro microperfusion study directly examined whether thyroid hormone affects passive solute flux and whether thyroid hormone could explain the developmental changes in PST paracellular permeability. Passive chloride transport was 62.1 ± 4.5, 23.1 ± 7.7, and 111.6 ± 5.6 pmol·mm-1·min-1 in PST from euthyroid, hypothyroid, and hypothyroid animals that received thyroid treatment, respectively (control different from hypothyroid and thyroid treatment at P < 0.05). This was due to a thyroid hormone-mediated change in chloride permeability ( PCl). Mannitol permeability was 3.65 + 1.03, -0.19 + 0.72, and 3.60 + 1.12 × 10-6 cm/s in PST from euthyroid animals, hypothyroid animals, and hypothyroid rabbits that received thyroid replacement, respectively ( P < 0.05 hypothyroid vs. euthyroid and thyroid replacement). We demonstrate that PST from hypothyroid animals have a higher passive PNa/ PCl and PHCO3/ PCl than euthyroid controls. Finally, we examined whether these changes in permeability were paralleled by a change in PST paracellular resistance. Resistance was measured by current injection and cable analysis. The resistance in PST from hypothyroid rabbits was 6.3 ± 0.8 Ω·cm2, which was not different from control of 4.8 ± 0.7 Ω·cm2, or 7.0 ± 0.7 Ω·cm2 in hypothyroid animals that received thyroid replacement. Therefore, the maturational increase in thyroid hormone levels does not fully explain the developmental changes in the paracellular pathway.


1992 ◽  
Vol 263 (1) ◽  
pp. F175-F179 ◽  
Author(s):  
E. Feraille ◽  
S. Marsy ◽  
L. Cheval ◽  
C. Barlet-Bas ◽  
C. Khadouri ◽  
...  

This study was aimed at identifying the renal sites of the antinatriuretic action of insulin by evaluating whether this hormone may alter the function of Na-K-ATPase in specific nephron segments. For this purpose, possible actions of insulin on the rate of 86Rb uptake were evaluated in vitro on single segments of proximal convoluted tubule (PCT), thick ascending limb, and collecting tubule microdissected from collagenase-treated kidneys of normal rats. Results indicate that physiological concentrations of insulin inhibited by 44% the initial rate of ouabain-sensitive 86Rb uptake in the medullary and cortical thick ascending limb, whereas it increased it by 40% in proximal tubules and by 60% in both cortical and medullary collecting tubules. The kinetics and dose dependence of insulin actions were different in the thick ascending limb, the PCT, and the collecting tubule, with the latter less sensitive but displaying an earlier response to insulin than the PCT and the thick ascending limb.


1988 ◽  
Vol 254 (1) ◽  
pp. F9-F14 ◽  
Author(s):  
M. Baum ◽  
S. R. Hays

The present in vitro microperfusion study examined the effect of protein kinase C activation on transport in the rabbit proximal convoluted tubule (PCT). PCT were perfused with an ultrafiltrate-like solution and were bathed in a serumlike albumin solution. Addition of 5 x 10(-8) and 5 x 10(-7) M bath phorbol 12-myristate 13-acetate, an activator of protein kinase C, inhibited volume absorption from 1.06 +/- 0.10 to 0.77 +/- 0.07 nl.mm-1.min-1 (P less than 0.05) and 0.76 +/- 0.14 to 0.48 +/- 0.08 nl.mm-1.min-1 (P less than 0.01), respectively. Bath phorbol 12-myristate 13-acetate (5 x 10(-9) M) had no effect on volume absorption (Jv, 0.82 +/- 0.13 to 0.81 +/- 0.12 nl.mm-1.min-1). In contrast, 5 x 10(-8) M bath 4 alpha-phorbol, an inactive phorbol that does not activate protein kinase C, had no effect on Jv (0.95 +/- 0.14 to 0.94 +/- 0.11 nl.mm-1.min-1). Bath L-alpha-dioctanoylglycerol (10(-4) M), another known activator of protein kinase C, inhibited volume absorption from 0.96 +/- 0.08 to 0.71 +/- 0.08 nl.mm-1.min-1 (P less than 0.001). A 10-fold lower concentration of L-alpha-dioctanoylglycerol (10(-5) M) had no effect on Jv (0.81 +/- 0.18 to 0.78 +/- 0.17 nl.mm-1.min-1). Both 5 x 10(-8) M phorbol 12-myristate 13-acetate and 10(-4) M L-alpha-dioctanoylglycerol inhibited glucose, bicarbonate, and chloride transport in the PCT. These data are consistent with protein kinase C activation playing a role in the modulation of proximal tubular transport.


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