Acidemia alone does not stimulate rat renal Na+-H+ antiporter activity

115

Increased Na/H antiporter activity has been demonstrated after in vivo chronic metabolic acidosis as well as in vitro acid preincubation of cultured rabbit renal tubule cells. To study the underlying molecular mechanisms of this adaptive increase in Na/H antiporter activity, the present studies examined the effect of low pH media on Na/H antiporter activity and mRNA abundance in cultured renal tubule cells. Na/H antiporter activity was increased by 60% in a mouse renal cortical tubule cell line (MCI'), and by 90% in an oppossum kidney cell line (OKP) after 24 h of preincubation in acid (low [HCO3J) media. The ethylisopropylamiloride sensitivity of the Na/H antiporters were different in these two cell lines (MCI' IC5 = 65 nM; OKP IC5o = 4.5 MM). In MCT cells, Na/H antiporter mRNA abundance measured by RNA blots increased by two-to fivefold after 24 h in low IHCO31 media. Na/H antiporter mRNA abundance was also increased in MCT cells with high CO2 preincubation as well as in rat renal cortex with in vivo chronic acid feeding. In contrast to renal epithelia, acid preincubation of NIH 3T3 fibroblasts led to suppression of Na/H antiporter activity. RNA blots of 3T3 fibroblasts revealed the same size Na/H antiporter transcript as in MCT cells. However, Na/H antiporter mRNA levels were suppressed by acid preincubation. These studies demonstrate differential regulation ofNa/H antiporter activity and mRNA abundance in renal epithelial cells and fibroblasts in response to an acidotic environment. (J.

Section: Resultsmentioning

confidence: 72%

Differential regulation of Na/H antiporter by acid in renal epithelial cells and fibroblasts.

Moe¹,

Miller²,

Horie³

et al. 1991

115

“…ent in the apical membrane (2-4), contributes to up to 40% of the overall proximal H' secretion in rat (5)(6)(7). Physiologic studies have revealed increased or reduced Na+/H+ antiport activity and bicarbonate reabsorption in the proximal tubule in response, respectively, to metabolic acidosis (8)(9)(10)(11)(12)(13)(14) or metabolic alkalosis (12,13). Changes in V,.…”

Section: Introductionmentioning

confidence: 99%

Expression and distribution of renal vacuolar proton-translocating adenosine triphosphatase in response to chronic acid and alkali loads in the rat.

Bastani¹,

Purcell²,

Hemken³

et al. 1991

196

141

Renal hydrogen ion excretion increases with chronic acid loads and decreases with alkali loads. We examined the mechanism of adaptation by analyzing vacuolar proton-translocating adenosine triphosphatase (H' ATPase) 31-kD subunit protein and mRNA levels, and immunocytochemical distribution in kidneys from rats subjected to acid or alkali loads for 1,3,5,7, and 14 d. Acid-and alkali-loaded rats exhibited adaptive responses in acid excretion, but showed no significant changes in H' ATPase protein or mRNA levels in either cortex or medulla. In contrast, there were profound adaptive changes in the immunocytochemical distribution of H' ATPase in collecting duct intercalated cells. In the medulla, H' ATPase staining in acidloaded rats shifted from cytoplasmic vesicles to plasma membrane, whereas in alkali-loaded rats, cytoplasmic vesicle staining was enhanced, and staining of plasma membrane disappeared. In the cortical collecting tubule, acid loading increased the number of intercalated cells showing enhanced apical H' ATPase staining and decreased the number of cells with basolateral or poorly polarized apical staining. The results indicate that both medulla and cortex participate in the adaptive response to acid and alkali loading by changing the steady-state distribution of H' ATPase, employing mechanisms that do not necessitate postulating interconversion of intercalated cells with opposing polarities. (J. Clin. Invest. 1991. 88:126-136.)

“…In respiratory acidosis, proximal tubule Na/H antiporter activity has also been shown to be increased both in the isolated proximal tubule perfused in vitro (15) and in proximal tubule cells grown in primary culture (16). Results from brush border vesicle studies have been less consistent than in metabolic acidosis (17)(18)(19). However, one study did find an increase in maximal transport capacity or Vi.…”

Section: Introductionmentioning

confidence: 99%

Expression of rat renal Na/H antiporter mRNA levels in response to respiratory and metabolic acidosis.

Krapf¹,

Pearce²,

Lynch³

et al. 1991

The mammalian proximal tubule is an important mediator of the renal adaptive response to systemic acidosis. In chronic metabolic and respiratory acidosis the bicarbonate reabsorptive (or proton secretory) capacity is increased. This increase is mediated, at least in part, by an increase in Vmax of the luminal Na/H antiporter. To determine whether this adaptation involves increased mRNA expression, Na/H antiporter mRNA levels were measured by Northern analysis in renal cortex of rats with metabolic (6 mmol/kg body wt NH4Cl for 2 or 5 d) and respiratory (10% CO2/air balanced for 2 or 5 d) acidosis and of normal, pair-fed rats. Na/H antiporter mRNA levels were unchanged after 2 d of both metabolic and respiratory acidosis. After 5 d, however, Na/H antiporter mRNA expression was increased 1.76 +/- 0.12-fold in response to metabolic acidosis (P less than 0.005, n = 8), but was not different from normal in response to respiratory acidosis: 1.1 +/- 0.2 (NS, n = 8). Thus, the renal adaptive response to metabolic acidosis involves increased cortical Na/H antiporter mRNA levels. In contrast, the enhanced proximal tubule Na/H antiporter activity and bicarbonate reabsorption in respiratory acidosis seem to involve mechanisms other than increased Na/H antiporter gene expression.