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The excretion of uromodulin is modulated by the calcium-sensing receptor


Tokonami, Natsuko; Olinger, Eric; Debaix, Huguette; Houillier, Pascal; Devuyst, Olivier (2018). The excretion of uromodulin is modulated by the calcium-sensing receptor. Kidney International, 94(5):882-886.

Abstract

Uromodulin is produced in the thick ascending limb, but little is known about regulation of its excretion in urine. Using mouse and cellular models, we demonstrate that excretion of uromodulin by thick ascending limb cells is increased or decreased upon inactivation or activation of the calcium-sensing receptor (CaSR), respectively. These effects reflect changes in uromodulin trafficking and likely involve alterations in intracellular cyclic adenosine monophosphate (cAMP) levels. Administration of the CaSR agonist cinacalcet led to a rapid reduction of urinary uromodulin excretion in healthy subjects. Modulation of uromodulin excretion by the CaSR may be clinically relevant considering the increasing use of CaSR modulators.

Abstract

Uromodulin is produced in the thick ascending limb, but little is known about regulation of its excretion in urine. Using mouse and cellular models, we demonstrate that excretion of uromodulin by thick ascending limb cells is increased or decreased upon inactivation or activation of the calcium-sensing receptor (CaSR), respectively. These effects reflect changes in uromodulin trafficking and likely involve alterations in intracellular cyclic adenosine monophosphate (cAMP) levels. Administration of the CaSR agonist cinacalcet led to a rapid reduction of urinary uromodulin excretion in healthy subjects. Modulation of uromodulin excretion by the CaSR may be clinically relevant considering the increasing use of CaSR modulators.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Physiology
07 Faculty of Science > Institute of Physiology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Uncontrolled Keywords:Nephrology
Language:English
Date:1 November 2018
Deposited On:11 Feb 2019 14:35
Last Modified:11 Feb 2019 17:06
Publisher:Elsevier
ISSN:0085-2538
OA Status:Green
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1016/j.kint.2018.07.022
PubMed ID:30348305
Project Information:
  • : FunderSNSF
  • : Grant IDP300P3_158521
  • : Project TitleInvestigation of new calcium sensing mechanisms in the kidney

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