Effect of parathyroid hormone on urinary acidification

Arruda, José A.L.; Nascimento, L.; Westenfelder, Christof; Kurtzman, Neil A.

doi:10.1152/ajprenal.1977.232.5.f429

Cited by 14 publications

(8 citation statements)

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“…PTH, the primary regulator of serum calcium and phosphate homeostasis, acts on the proximal tubule, the thick ascending limb, and the distal convoluted tubule to alter urinary electrolyte and fluid excretion (1,2,7,14,15,17). PTH has a potent inhibitory effect on NHE3.…”

Section: Namentioning

confidence: 99%

Mechanisms underlying the long-term regulation of NHE3 by parathyroid hormone

Bezerra¹,

Girardi²,

Carraro‐Lacroix³

et al. 2008

American Journal of Physiology-Renal Physiology

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Bezerra CN, Girardi AC, Carraro-Lacroix LR, Rebouças NA. Mechanisms underlying the long-term regulation of NHE3 by parathyroid hormone. Am J Physiol Renal Physiol 294: F1232-F1237, 2008. First published March 5, 2008 doi:10.1152/ajprenal.00025.2007The activity of the Na ϩ /H ϩ exchanger NHE3 is regulated by a number of factors including parathyroid hormone (PTH). In the current study, we used a renal epithelial cell line, the opossum kidney (OKP) cell, to elucidate the mechanisms underlying the long-term effects of PTH on NHE3 transport activity and expression. We observed that NHE3 activity was reduced 6 h after addition of PTH, and this reduction persisted almost unaltered after 24 h. The decrease in activity was associated with diminished NHE3 cell surface expression at 6, 16, and 24 h after PTH addition, total cellular NHE3 protein at 16 and 24 h, and NHE3 mRNA abundance at 24 h. The lower levels of NHE3 mRNA were associated to a small, but significant, decrease in mRNA stability. Additionally, by analyzing the rat NHE3 gene promoter activity in OKP cells, we verified that the regulatory region spanning the segment Ϫ152 to ϩ55 was mildly reduced under the influence of PTH. This effect was completely abolished by the presence of the PKA inhibitor KT 5720. In conclusion, long-term exposure to PTH results in reduction of NHE3 mRNA levels due to a PKA-dependent inhibitory effect on the NHE3 promoter and a small reduction of mRNA half-life, and decrease in the total amount of protein which is preceded by endocytosis of the apical surface NHE3. The decreased NHE3 expression is likely to be responsible for the reduction of sodium, bicarbonate, and fluid reabsorption in the proximal tubule consistently perceived in experimental models of PTH disorders. Naϩ /H ϩ exchange; proximal tubule; hyperparathyroidism; surface expression; promoter activity THE HUMAN BODY has a remarkable ability to maintain precise control of its acid-base and volume status. Although multiple mechanisms throughout the body contribute to this process, the renal proximal tubule plays a fundamental role, since it is responsible for reabsorption of the majority of the filtered sodium, bicarbonate, chloride, and water. Two-thirds of the transcellular NaHCO 3 reabsorption are mediated by proton secretion through the apical membrane Na ϩ /H ϩ exchanger, NHE3 (4, 21), and most of NaCl reabsorption is indirectly related to it. This transporter thereby plays an important role in the maintenance of fluid, electrolyte, and acid-base balance, and its activity is regulated in response to a wide variety of acute and chronic changes in physiological parameters (29,(31)(32)(33).The kidney is one of the major target organs for parathyroid hormone (PTH). PTH, the primary regulator of serum calcium and phosphate homeostasis, acts on the proximal tubule, the thick ascending limb, and the distal convoluted tubule to alter urinary electrolyte and fluid excretion (1,2,7,14,15,17). PTH has a potent inhibitory effect on NHE3. The acute inhibition of NHE3 by PTH has be...

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Section: Namentioning

confidence: 99%

Mechanisms underlying the long-term regulation of NHE3 by parathyroid hormone

Bezerra¹,

Girardi²,

Carraro‐Lacroix³

et al. 2008

American Journal of Physiology-Renal Physiology

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“…More recently, it has been suggested that measurement of the urine to blood (U-B) Pco2 gradient in alkaline urine can be used to assess distal hydrogen ion secretion (2)(3)(4). We have recently demonstrated that in highly alkaline urine (urine pH > 7.8), U-B Pco2 is not influenced by acute decreases in glomerular filtration rate (GFR), urine flow, bicarbonate excretion, phosphate concentration and excretion, and parathyroid hormone administration (4,5). The failure of U-B Pco2 to rise with alkalinization of the urine has been taken as evidence of a distal acidification defect (2,4).…”

Section: Introductionmentioning

confidence: 99%

The Critical Importance of Urinary Concentrating Ability in the Generation of Urinary Carbon Dioxide Tension

Arruda¹,

Nascimento²,

Mehta³

et al. 1977

J. Clin. Invest.

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A B S T RA C T Measurement of urine to blood (U-B) carbon dioxide tension (Pco2) gradient during alkalinization of the urine has been suggested to assess distal H+ secretion. A fact that has not been considered in previous studies dealing with urinary Pco2 is that dissolution of HCO3 in water results in elevation of Pco2 which is directly proportional to the HCO3 concentration. To investigate the interrelationship of urinary HCO3 and urinary acidification, we measured U-B Pco2 in (a) the presence of enhanced H+ secretion and decreased concentrating ability i.e., chronic renal failure (CRF), (b) animals with normal H+ secretion and decreased concentrating ability, Brattleboro (BB) rats, and (c) the presence of both impaired H+ secretion and concentrating ability (LiCl treatment and after release of unilateral ureteral obstruction). At moderately elevated plasma HCO3 levels (30-40 meq/liter), normal rats achieved a highly alkaline urine (urine pH > 7.8) and raised urine HCO3 concentration and U-B Pco2. At similar plasma HCO3 levels, BB rats had a much higher fractional water excretion and failed to raise urine pH, urine HCO3 concentration, and U-B Pco2 normally. At a very high plasma HCO3 (>50 meq/liter), BB rats raised urine pH, urine HCO3 concentration, and U-B Pco2 to the same levels seen in normals. CRF rats failed to raise urine pH, urine HCO3, and U-B Pco2 normally at moderately elevated plasma HCO3 levels; at very high plasma HCO3 levels, CRF rats achieved a highly alkaline urine but failed to raise U-B Pco2. Dogs and patients with CRF were also unable to raise urine pH, urine HCO3 concentration, and U-B Pco2 normally at moderately elevated plasma HCO3 levels. In rats, dogs, and man, U-B Pco2 was directly related to urine HCO3 concentration and inversely related to fractional water excretion. At moderately elevated plasma HCO3 levels, animals with a distal acidification defect failed to raise U-B Pco2; increasing the plasma HCO3 to very high levels resulted in a significant increase in urine HCO3 concentration and U-B Pco2. The observed urinary Pco2 was very close to the Pco2 which would be expected by simple dissolution of a comparable amount of HCO3 in water. These data demonstrate that, in highly alkaline urine, urinary Pco2 is largely determined by concentration of urinary HCO3 and cannot be used as solely indicating distal H+ secretion.

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“…Numer ous clearance and micropuncture studies have demon strated a direct effect of PTH on the proximal renal tubule acting to inhibit bicarbonate reabsorption [1][2][3][4][5][6]. The net effect seems to be small at normal serum bicarbonate con centrations, suggesting that PTH induced bicarbonate wasting does not give rise to frank metabolic acidosis under ordinary circumstances.…”

Section: Discussionmentioning

confidence: 99%

“…Magnesium remained stable but serum potassium fell in response to EDTA. These observations suggest that endogenous PTH can significantly affect plasma bicarbonate in vivo and may contribute to post renal transplant renal tubular acidosis.Numerous clearance and micropuncture studies docu ment an inhibitory effect of parathyroid hormone PTH on the renal tubular reabsorption of bicarbonate [1][2][3][4][5][6]. Although renal bicarbonate wasting and hyperchloremic metabolic acidosis may result, they are not usually promi nent features of primary hyperparathyroidism [7][8][9][10].…”

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Change in Serum Bicarbonate during Acute EDTA Infusions in Post-Transplant Hyperparathyroidism

Muther¹,

McCarron²,

Bennett³

1982

Nephron

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We evaluated the effect of endogenous parathyroid hormone (PTH) on serum bicarbonate in 12 patients with postrenal transplant hyperparathyroidism. EDTA-induced hypocalcemia produced a significant rise in serum PTH (p < 0.001). Associated with the increase in PTH was a significant fall in plasma bicarbonate (p < 0.001) and increase in the chloride: phosphorus ratio (p < 0.001). Magnesium remained stable but serum potassium fell in response to EDTA. These observations suggest that endogenous PTH can significantly affect plasma bicarbonate in vivo and may contribute to post renal transplant renal tubular acidosis.

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Effect of parathyroid hormone on urinary acidification

Cited by 14 publications

References 0 publications

Mechanisms underlying the long-term regulation of NHE3 by parathyroid hormone

Mechanisms underlying the long-term regulation of NHE3 by parathyroid hormone

The Critical Importance of Urinary Concentrating Ability in the Generation of Urinary Carbon Dioxide Tension

Change in Serum Bicarbonate during Acute EDTA Infusions in Post-Transplant Hyperparathyroidism

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