Upregulation of collecting duct aquaporin-2 by metabolic acidosis: role of vasopressin

Abstract

Amlal, Hassane, Sulaiman Sheriff, and Manoocher Soleimani. Upregulation of collecting duct aquaporin-2 by metabolic acidosis: role of vasopressin. Am J Physiol Cell Physiol 286: C1019-C1030, 2004. First published December 24, 2003 10.1152/ ajpcell.00394.2003.-Metabolic acidosis is associated with alteration in fluid and electrolyte reabsorption in a number of nephron segments. However, the effects of metabolic acidosis on urine osmolality and aquaporin-2 (AQP-2) remain poorly understood. In these studies, we examined the effects of chronic metabolic acidosis on water handling by the kidney. Rats were placed in metabolic cages and subjected to water (control) or 280 mM NH4Cl loading for 120 h to induce metabolic acidosis. The results indicated a significant increase in urine osmolality with no change in urine volume or urinary Na ϩ excretion in acid-loaded animals. This effect was independent of alteration in fluid intake or salt/Cl Ϫ loading. Immunoblotting and Northern hybridization studies indicated that AQP-2 protein abundance and mRNA expression levels increased significantly along the collecting duct system of NH4Cl-but not NaCl-loaded animals. RIA results indicated that metabolic acidosis was associated with a fourfold increase in circulating levels of vasopressin (AVP) and a significant increase in brain AVP mRNA expression levels. In conclusion, metabolic acidosis upregulates the expression levels of AQP-2 and increases urine osmolality, suggesting an adaptive increase in water reabsorption in the collecting duct. A concomitant increase in AVP synthesis and secretion likely plays an essential role in the adaptation of AQP-2 in metabolic acidosis.kidney; acid-base; urine osmolality; sodium excretion rate SEVERAL STUDIES HAVE EXAMINED the effect of metabolic acidosis on fluid and electrolyte reabsorption in various nephron segments. Chronic metabolic acidosis increased HCO 3 Ϫ reabsorption in the proximal tubule (1,19,27), medullary thick ascending limb (mTAL) (20), and collecting duct (10, 46). In proximal and mTAL tubules, the increase in HCO 3 Ϫ reabsorption in acidosis was predominantly mediated via upregulation of the apical Na ϩ /H ϩ exchanger (NHE3) (2, 29, 53). Interestingly and despite an increase in HCO 3 Ϫ reabsorption, metabolic acidosis was consistently shown to decrease water and NaCl reabsorption in the proximal tubule (30,43,51). The decrease in Na ϩ reabsorption was attributed to the downregulation of organic anion pathways that are coupled to apical NHE3 (51), Na ϩ -dependent inorganic sulfate (Na-S i ) cotransporter (40), and Na ϩ -phosphate cotransporter (NaP i -2) (7). Despite the known effects on ion transporters in the proximal tubule and mTAL, little is known about the effect of metabolic acidosis on water transport in the collecting duct. Recent studies examined the effects of metabolic acidosis on V1a and V2 vasopressin (AVP) receptors in the kidney and reported an increase in V1a and a downregulation of V2 expression in response to metabolic acidosis (48). These studies, however...

The phosphorylation state of serine 256 is dominant over that of serine 261 in the regulation of AQP2 trafficking in renal epithelial cells

“…Experiments using simultaneous mutations of S256 and S261 showed that the phosphorylation or dephosphorylation state of S261 does not alter the dominant effect driven by the phosphorylation and dephosphorylation state of S256 in VP-induced AQP2 trafficking. It remains possible that the effects that we have observed in our transfected cell model may not exactly mimic AQP2 trafficking in principal cells in vivo in this instance, although LLC-PK cells have proven to be a reliable predictor of the in vivo AQP2 signaling machinery in many previous studies (1,2,7,12,(21)(22)(23)(24)(25). Also, it is possible that more subtle kinetic differences in the intracellular trafficking pathway of AQP2 occur that were not detectable using the present techniques.…”

Acute and chronic metabolic acidosis interferes with aquaporin-2 translocation in the rat kidney collecting ducts

“…However, the 0.28 M NH 4 Cl solution is hypertonic and will cause an increase in plasma osmolality and a subsequent stimulation of the plasma level of vasopressin. 12,13 The drinking method of the 0.28 M NH 4 Cl solution will also decrease the appetite and body weight of rats compared with that of control rats. Taken together, the drinking method of the 0.28 M NH 4 Cl solution induces metabolic acidosis with dehydration.…”

“…11 However, it is not known whether metabolic acidosis affects AQP2 expression in the kidney. Recently, Amlal et al 12 reported that metabolic acidosis increased AQP2 expression in the collecting ducts by the activation of plasma vasopressin level. They used a 0.28 M NH 4 Cl solution for the induction of metabolic acidosis.…”

Acid-Base Status Determines the Renal Expression of Ca2+ and Mg2+ Transport Proteins

“…Earlier studies, including micropuncture experiments, suggested that systemic acid-base disturbances specifically influence Ca 2ϩ and Mg 2ϩ reabsorption in DCT/CNT (2,10). Hypothetically, regulation of Ca 2ϩ and Mg 2ϩ transport proteins in these nephron segments could be involved in the altered renal divalent excretion secondary to changes in acid-base status, as was shown for other renal transporters and channels (11)(12)(13)(14). We previously demonstrated that tacrolimus (FK506)-induced Ca 2ϩ and Mg 2ϩ wasting as well as thiazide-induced hypomag-nesemia are associated with decreased renal expression of Ca 2ϩ and/or Mg 2ϩ transporters (15,16).…”