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Calcium receptor signaling and citrate transport

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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 → Gq → PKC signaling pathway. Thus, the CaSR may decrease the propensity for stone formation via actions in both proximal and distal nephron segments.

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Notes

  1. 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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Acknowledgements

This work was supported by NIH/NIDDK RO1 DK095879 to Dr. Hering-Smith.

Funding

This study was funded by NIH/NIDDK RO1 DK095879 to Dr. Hering-Smith. Dr. Hering-Smith is also supported by the NIH Louisiana Clinical and Translational Sciences Center (LA CaTS) grant.

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Authors and Affiliations

  1. Nephrology and Hypertension 8545, Tulane University School of Medicine, 1430 Tulane Avenue, New Orleans, LA, 70112, USA

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

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  1. Ryan W. Walker
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  2. Shijia Zhang
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  3. Joycelynn A. Coleman-Barnett
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  4. L. Lee Hamm
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Correspondence to Kathleen S. Hering-Smith.

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Dr. Ryan Walker declares that he has no conflict of interest. Dr. Shijia Zhang declares that he has no conflict of interest. Ms. Joycelynn Coleman-Barnett declares that she has no conflict of interest. Dr. L. Lee Hamm declares that he has no conflict of interest. Dr. Kathleen Hering-Smith declares that she has no conflict of interest.

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Walker, R.W., Zhang, S., Coleman-Barnett, J.A. et al. Calcium receptor signaling and citrate transport. Urolithiasis 46, 409–418 (2018). https://doi.org/10.1007/s00240-018-1035-0

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