BoneKEy Reports | BoneKEy Watch
Calcium-sensing receptor regulates blood calcium independent of PTH
DOI:10.1038/bonekey.2012.246
Parathyroid hormone (PTH) is a key factor that determines calcium (Ca) levels in the blood. PTH secretion is under the control of the Ca2+-sensing receptor (CaSR), which is expressed by, and acts within, parathyroid cells. The role of extraparathyroid CaSR is investigated here for the first time using thyroparathyroidectomized rats given PTH supplements.
When the rats were treated with a potent CaSR blocker, blood Ca concentration and renal tubular Ca absorption both increased but there was no change in PTH secretion and intestinal Ca absorption was unaffected. The same effect was noted in animals pretreated with bisphosphonates, indicating that bone Ca was not being released.
Immunostaining studies using two labeled CaSR antibodies revealed the location of the CaSR within rat kidney renal tubules, in the portion identified as the thick ascending loop of Henle (TAL) by co-staining with a TAL-specific antibody. Confirmation that CaSR expression takes place only in the TAL was obtained in a functional study looking at how CaSR agonists were able to affect Ca signaling in isolated and microperfused cortical TAL or cortical collecting ducts (CCD). The agonists produced a significant increase in the concentration of Ca ions in the cytosol of the isolated TALs but not in the CCDs.
Editor’s comment: This study provides further evidence that CaSR plays an autonomous role in serum Ca regulation by the kidney, acting independently of PTH, intestinal absorption and bone resorption. More provocatively, it demonstrates that CaSR is exclusively expressed in the TAL in both rodents and humans. This is contrary to previous studies that located the CaSR along the nephron and will force us (and the physiology books) to reconsider how serum Ca transport is actually regulated.
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