Role of the Na+/H+ antiporter in rat proximal tubule bicarbonate absorption.

Preisig, Patricia A.; Ives, Harlan E.; Cragoe, Edward J.; Alpern, Robert J.; Rector, Floyd C.

doi:10.1172/jci113190

Cited by 161 publications

(113 citation statements)

References 47 publications

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“…These results are consistent with impairment of bicarbonate absorption by this specific inhibitor ofsodium-hydrogen ion exchange. The observation that EIPA, a potent and specific blocker ofsodium-hydrogen exchange, does not significantly affect late distal tubule fluid absorption is consistent with (a) the absence of an important component of sodiumhydrogen exchange; and (b) no significant action of EIPA on sodium channels (25). S, solutions; low CI-solutions, Cl-substituted by gluconate, see Table I for explanation.…”

Section: Methodssupporting

confidence: 57%

Renal bicarbonate reabsorption in the rat. IV. Bicarbonate transport mechanisms in the early and late distal tubule.

Wang¹,

Malnic²,

Giebisch³

et al. 1993

J. Clin. Invest.

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Bicarbonate transport was studied in vivo by separate microperfusion experiments of early and late distal tubules. Total CO2 was measured by microcalorimetry and fluid absorption by 3H-inulin. Significant bicarbonate absorption was observed in all experimental conditions. Bicarbonate transport was loaddependent upon increasing the luminal bicarbonate concentration from 15 to 50 mM in both early and late distal tubule segments and remained constant at higher concentrations at a maximum rate of 100-110 pmol/min per mm. At low lumen bicarbonate concentrations (15 mM), higher rates of bicarbonate absorption were observed in early (32.9±4.57 pmol/min per mm) as compared to late distal tubules (10.7±3.1 pmol/ min per mm). Amiloride and ethyl-isopropylamiloride both inhibited early but not late distal tubule bicarbonate absorption whereas acetazolamide blocked bicarbonate transport in both tubule segments. Fluid absorption was significantly reduced in both tubule segments by amiloride but only in early distal tubules by ethyl-isopropylamiloride. Substitution of lumen chloride by gluconate increased bicarbonate absorption in late but not in early distal tubules. Bafilomycin Al, an inhibitor of HATPase, inhibited late and also early distal tubule bicarbonate absorption, the latter at higher concentration. After 8 d on a low K diet, bicarbonate absorption increased significantly in both early and late distal tubules. Schering compound 28080, a potent H-K ATPase inhibitor, completely blocked this increment of bicarbonate absorption in late but not in early distal tubule. The data suggest bicarbonate absorption via Na+-H+ exchange and H-ATPase in early, but only by amiloride-insensitive H' secretion (H-ATPase) in late distal tubules. The study also provides evidence for activation of K+-H+ exchange in late distal tubules of K depleted rats. Indirect evidence implies a component of chloride-dependent bicarbonate secretion in late distal tubules and suggests that net bicarbonate transport at this site results from bidirectional bicarbonate movement. (J. Clin.

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Section: Methodssupporting

confidence: 57%

Renal bicarbonate reabsorption in the rat. IV. Bicarbonate transport mechanisms in the early and late distal tubule.

Wang¹,

Malnic²,

Giebisch³

et al. 1993

J. Clin. Invest.

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“…It is therefore essential in the regulation of extracellular volume homeostasis and therefore blood pressure. 11,12 Enhanced sodium reabsorption in this segment of the nephron is implicated in the …”

Section: Discussionmentioning

confidence: 99%

“…11,12 It is also involved in reabsorbing most of the filtered bicarbonate via sodium/ hydrogen exchanger 3 (NHE3). 13 Enhanced sodium and fluid absorption by this nephron segment has been linked to hypertension in humans and several animal models.…”

mentioning

confidence: 99%

Fructose Stimulates Na/H Exchange Activity and Sensitizes the Proximal Tubule to Angiotensin II

et al. 2014

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Abstract-The proximal nephron reabsorbs 60% to 70% of the fluid and sodium and most of the filtered bicarbonate via Na/H exchanger 3. Enhanced proximal nephron transport is implicated in hypertension. Our findings show that a fructose-enriched diet causes salt sensitivity. We hypothesized that fructose stimulates luminal Na/H exchange activity and sensitizes the proximal tubule to angiotensin II. Na/H exchange was measured in rat proximal tubules as the rate of intracellular pH (pH i ) recovery in fluorescent units/s. Replacing 5 mmol/L glucose with 5 mmol/L fructose increased the rate of pH i recovery (1.8±0.6 fluorescent units/s; P<0.02; n=8). Staurosporine, a protein kinase C inhibitor, blocked this effect. We studied whether this effect was because of the addition of fructose or removal of glucose. The basal rate of pH i recovery was first tested in the presence of a 0.6-mmol/L glucose and 1, 3, or 5 mmol/L fructose added in a second period. The rate of pH i recovery did not change with 1 mmol/L but it increased with 3 and 5 mmol/L of fructose. Adding 5 mmol/L glucose caused no change. Removal of luminal sodium blocked pH i recovery. With 5.5 mmol/L glucose, angiotensin II (1 pmol/L) did not affect the rate of pH i recovery (change, -1.1±0.5 fluorescent units/s; n=9) but it increased the rate of pH i recovery with 0.6 mmol/L glucose/5 mmol/L fructose (change, 4.0±2.2 fluorescent units/s; P<0.02; n=6). We conclude that fructose stimulates Na/H exchange activity and sensitizes the proximal tubule to angiotensin II. This mechanism is likely dependent on protein kinase C. These results may partially explain the mechanism by which a fructose diet induces

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“…In the proximal tubule, NHE3 provides a major route of luminal sodium transport across the membrane, whereas NBC1 serves as the exit across the basolateral membrane (Mahnensmith & Aronson, 1985;Preisig et al, 1987;Soleimani et al, 1987). On the other hand, OAT plays a crucial role in the excretion of a variety of potentially toxic compounds in the proximal tubule (van Montfoort et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Decreased Expression of Na+/K+-ATPase, NHE3, NBC1, AQP1 and OAT in Gentamicin-induced Nephropathy

Bae

Lee

Park

et al. 2008

Korean J Physiol Pharmacol

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Role of the Na+/H+ antiporter in rat proximal tubule bicarbonate absorption.

Cited by 161 publications

References 47 publications

Renal bicarbonate reabsorption in the rat. IV. Bicarbonate transport mechanisms in the early and late distal tubule.

Renal bicarbonate reabsorption in the rat. IV. Bicarbonate transport mechanisms in the early and late distal tubule.

Fructose Stimulates Na/H Exchange Activity and Sensitizes the Proximal Tubule to Angiotensin II

Decreased Expression of Na+/K+-ATPase, NHE3, NBC1, AQP1 and OAT in Gentamicin-induced Nephropathy

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