Effects of parathyroid hormone and calcitonin on Na+, Cl−, K+, Mg2+ and Ca2+ transport in cortical and medullary thick ascending limbs of mouse kidney

Abstract

The effect of parathyroid hormone (PTH) on transepithelial Na+, Cl-, K+, Ca2+ and Mg2+ transport was investigated in isolated perfused cortical thick ascending limbs (cTAL) and that of human calcitonin (hCT) was tested in both cortical and medullary thick ascending limbs (mTAL) of the mouse nephron. The transepithelial ion net fluxes (Jx) were determined by electron probe analysis of the perfused and collected fluids. Simultaneously, the transepithelial voltage (PDte) and resistance (Rte) were recorded. In cTAL segments, PTH and hCT significantly stimulated the reabsorption of Na+, Cl-, Ca2+ and Mg2+, hCT generated a net K+ secretion towards the lumen and PTH tended to exert the same effect. Neither PDte nor Rte were significantly altered by either PTH or hCT. However, in the post-experimental period a significant decrease in PDte was noted. Time control experiments carried out under similar conditions revealed a significant decrease in PDte with time, which could have masked the hormonal response. In mTAL segments, Mg2+ and Ca2+ transport was close to zero, hCT did not exert any detectable effect on either PDte or Jcl-, JNa+, JK+, JMg2+ and JCa2+ in these segments. In conclusion, our data demonstrate that PTH and hCT stimulate NaCl reabsorption as well as Mg2+ and Ca2+ reabsorption in the cTAL segment of the mouse. These data are in agreement with and extend data obtained in vivo in the rat.

Calcitonin-stimulated renal Ca2+ reabsorption occurs independently of TRPV5

“…In addition, the urinary Na + /K + ratio remained unchanged excluding an effect on the collecting duct. These data are consistent with a primary effect of CT on electrolyte transport in the TAL and DCT [5][6][7]17]. …”

“…Administration of CT to rats increases the renal reabsorption of Ca 2+ , which is in part achieved by increasing the reabsorption of Ca 2+ in the TAL. Here, application of CT also increases vectorial NaCl transport [5][6][7]. Active transcellular Ca 2+ transport is restricted to the distal convolutions.…”

Molecular Physiology and Pathophysiology of Electroneutral Cation-Chloride Cotransporters

“…In addition, as discussed in section IIIB, in mice, the stimulatory effect of vasopressin on BSC1/NKCC2 trafficking appears to be related to inhibition by cAMP of a dominant-negative effect of the 770-amino acid short isoform BSC1-S on trafficking of fulllength isoform BSC1/NKCC2 (269,325). Other hormones that generate cAMP via their respective G s -coupled receptors stimulate concomitant increases in NaCl absorption rate, such as parathyroid hormone, calcitonin, and glucagons, presumably using similar mechanisms to those demonstrated for vasopressin (89,103,286). Prostaglandin E 2 has been demonstrated to have a short-term inhibitory effect on NaCl absorption in TALH (387), presumably via its ability to inhibit cAMP production in TALH cells (402).…”

Physiology and pathophysiology of the calcium-sensing receptor in the kidney

“…Basolateral, but not urinary, increases in plasma Ca 2ϩ (or Mg 2ϩ ) concentrations diminish their own reabsorption (128). Indeed, in the TAL, the bulk of the divalent cation reabsorption proceeds through the paracellular pathway and is proportional to the transtubular electrochemical driving force (35). This, in turn, is heavily reliant on the rate and extent of Na ϩ reabsorption.…”