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Urolithiasis

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30.01.2018 | Original Paper

Calcium receptor signaling and citrate transport

verfasst von: Ryan W. Walker, Shijia Zhang, Joycelynn A. Coleman-Barnett, L. Lee Hamm, Kathleen S. Hering-Smith

Erschienen in: Urolithiasis | Ausgabe 5/2018

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Abstract

The calcium sensing receptor (CaSR) in the distal nephron decreases the propensity for calcium stones. Here we investigate if the apical CaSR in the proximal tubule also prevents stone formation acting via regulation of apical dicarboxylate and citrate transport. Urinary citrate, partially reabsorbed as a dicarboxylate in the proximal tubule lumen, inhibits stone formation by complexing calcium. We previously demonstrated a novel apical calcium-sensitive dicarboxylate transport system in OK proximal tubule cells. This calcium-sensitive process has the potential to modulate the amount of citrate available to complex increased urinary calcium. Using isotope labeled succinate uptake in OK cells along with various pharmacologic tools we examined whether the CaSR alters apical dicarboxylate transport and through which signal transduction pathways this occurs. Our results indicate that in the proximal tubule CaSR adjusts apical dicarboxylate transport, and does so via a CaSR → G_q → PKC signaling pathway. Thus, the CaSR may decrease the propensity for stone formation via actions in both proximal and distal nephron segments.

Complicating this interpretation, NaDC1 has been considered responsible for all citrate reabsrorption on the apical side of the proximal tube. We have previously shown that NaDC1 ex vivo is not calcium-sensitive. So whether the calcium sensitive transport is NaDC1 or not remains unknown.

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Titel: Calcium receptor signaling and citrate transport
verfasst von: Ryan W. Walker
Shijia Zhang
Joycelynn A. Coleman-Barnett
L. Lee Hamm
Kathleen S. Hering-Smith
Publikationsdatum: 30.01.2018
Verlag: Springer Berlin Heidelberg
Erschienen in: Urolithiasis / Ausgabe 5/2018
Print ISSN: 2194-7228
Elektronische ISSN: 2194-7236
DOI: https://doi.org/10.1007/s00240-018-1035-0

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