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

Natsuko Tokonami; Eric Olinger; Huguette Debaix; Pascal Houillier; Olivier Devuyst

doi:10.1016/j.kint.2018.07.022

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

Kidney Int. 2018 Nov;94(5):882-886. doi: 10.1016/j.kint.2018.07.022.

Authors

Natsuko Tokonami¹, Eric Olinger¹, Huguette Debaix¹, Pascal Houillier², Olivier Devuyst³

Affiliations

¹ Institute of Physiology, University of Zurich, Zurich, Switzerland.
² Sorbonne Université, UPMC Univ Paris 06, INSERM, Université Paris Descartes, UMR_S 1138 Team 3, Centre de Recherche des Cordeliers, Paris, France.
³ Institute of Physiology, University of Zurich, Zurich, Switzerland. Electronic address: [email protected].

PMID: 30348305
DOI: 10.1016/j.kint.2018.07.022

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.

Keywords: TAL; distal tubule; mineral metabolism; signaling; vasopressin.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Calcium / metabolism
Cyclic AMP / analysis
Loop of Henle / metabolism
Mice
Receptors, Calcium-Sensing / genetics
Receptors, Calcium-Sensing / physiology*
Uromodulin / urine*

Substances

Receptors, Calcium-Sensing
Uromodulin
Cyclic AMP
Calcium