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The calcium-sensing receptor regulates calcium absorption in MDCK cells by inhibition of PMCA

K A Blankenship1, J J Williams, M S Lawrence

  • 1Molecular Signaling Group and Departments of Medicine and Biochemistry and Molecular Biology, The University of Louisville, Louisville, KY 40202, USA.

American Journal of Physiology. Renal Physiology
|April 9, 2001
PubMed

Insights

The calcium-sensing receptor (CaR) inhibits calcium transport in kidney cells. This occurs via a phospholipase C (PLC) pathway that also reduces plasma membrane calcium ATPase (PMCA) activity.

Area of Science:

  • Nephrology
  • Cell Physiology
  • Molecular Biology

Background:

  • Calcium homeostasis is tightly regulated in the kidneys.
  • The calcium-sensing receptor (CaR) plays a crucial role in modulating calcium levels.
  • Understanding CaR signaling in renal cells is vital for kidney function.

Purpose of the Study:

  • To investigate the effect of CaR stimulation on calcium transport in kidney cells.
  • To elucidate the signaling pathway involved in CaR-mediated inhibition of calcium transport.
  • To determine if CaR affects the activity of plasma membrane calcium ATPase (PMCA).

Main Methods:

  • Utilized Madin-Darby canine kidney (MDCK) cell monolayers.
  • Measured calcium transport across the cell monolayer.
  • Stimulated the CaR with agonists and assessed effects on transport, voltage, and resistance.
  • Investigated the role of phospholipase C (PLC) and pertussis toxin.
  • Assayed plasma membrane calcium ATPase (PMCA) activity.

Main Results:

  • CaR stimulation inhibited calcium transport in a time- and concentration-dependent manner.
  • This inhibition was independent of transepithelial voltage and resistance changes.
  • The effect was blocked by the PLC inhibitor U-73122, but not by pertussis toxin.
  • CaR stimulation led to a PLC-dependent inhibition of PMCA activity.

Conclusions:

  • CaR activation inhibits transcellular calcium absorption in a kidney cell model.
  • The mechanism involves a phospholipase C (PLC) dependent pathway.
  • CaR inhibits calcium transport by reducing plasma membrane calcium ATPase (PMCA) activity.

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