Effects of parathyroid hormone on renal tubular calcium and phosphate handling

Abstract

Central to the maintenance of calcium homeostasis is the regulated reabsorption of calcium along the nephron. To this end, parathyroid hormone (PTH) is released from the parathyroid gland in response to lowered plasma calcium levels. This hormone acts through the PTH 1 receptor along the nephron to increase urinary phosphate excretion and decrease urinary calcium excretion. In the proximal tubule, PTH inhibits phosphate reabsorption by reducing the abundance of sodium phosphate cotransporters in the apical membrane. PTH likely decreases calcium reabsorption from the proximal tubule, by reducing the reabsorption of sodium, an event necessary for the paracellular movement of calcium across this segment. In the thick ascending limb (TAL), PTH increases calcium permeability and may increase the electrical driving force thereby increasing calcium reabsorption in the TAL. Finally, in the distal convolution, PTH acts to increase transcellular calcium reabsorption by increasing the activity and abundance of the apically expressed calcium channel TRPV5.

Inhibition of pannexin‐1 does not restore electrolyte balance in precystic Pkd1 knockout mice

“…This was paralleled by a significant increase in urinary P i excretion in iKsp-Pkd1 −/− mice compared to control mice (P genotype = 0.046) (Figure 5b). Renal P i reabsorption occurs for 80% in the proximal tubule and is mediated by the apical transporters Na + -dependent phosphate transporter 2A (Napi2a; encoded by Slc34a1), Na + -dependent phosphate transporter 2C (Napi2c; encoded by Slc34a3) and Na + -dependent phosphate transporter 2 (Pit-2; encoded by Slc20a2) (Alexander & Dimke, 2023). Slc34a1 expression was not significantly different between control and iKsp-Pkd1 −/− mice or between vehicle-and BB-FCF-treated animals F I G U R E 2 Unaltered expression of claudins involved in paracellular Ca 2+ and Mg 2+ reabsorption.…”

Molecular mechanisms of loop diuretics on renal calcium and magnesium transport

“…4 Divalent cation reabsorption occurs via the paracellular pathway in the cortical portion of the segment, in a process that is critically dependent on the formation of a lumen-positive voltage gradient. 4 The electrical gradient is created by the transport of sodium, potassium, and chloride ions in the TAL. This process is driven by the coordinated interaction of the NKCC2 cotransporter, ROMK, CLC-Kb channels, and the Na + /K + -ATPase (Figure 1A).…”

“…The TAL is an important site for reabsorbing both calcium and magnesium, with this segment being responsible for reclaiming 25% of filtered calcium and 60% of filtered magnesium 4 . Divalent cation reabsorption occurs via the paracellular pathway in the cortical portion of the segment, in a process that is critically dependent on the formation of a lumen‐positive voltage gradient 4 . The electrical gradient is created by the transport of sodium, potassium, and chloride ions in the TAL.…”

“…This process is driven by the coordinated interaction of the NKCC2 cotransporter, ROMK, CLC‐Kb channels, and the Na + /K + ‐ATPase (Figure 1A). 4 The transepithelial voltage generated by this process is critical for the paracellular reclamation of calcium and magnesium. Claudins, which are tight junction proteins, in particularly CLDN16 and CLDN19, allow the permeation of calcium and magnesium from this segment.…”

Kidney membrane proteins and epithelial transport

“…2 In this special series on membrane proteins, epithelial transport, and kidney physiology, we share a number of high-quality reviews that serve as a valuable resource for researchers to offer comprehensive insights into the latest developments in these fields. These include pertinent reviews on the role of the mesangium in glomerular function, 3 the importance of mTOR signaling in regulating renal ion transport, 4 an extensive overview of uric acid transport and the pharmacological targeting of these transporters, 5 a delineation of the effects of parathyroid hormone on calcium and phosphate handling in the kidney, 6 and how SGLT2 inhibitors are able to protect the kidney. 7 With the outlook of more reviews on the way, the series is open for submissions and suggestions for reviews.…”