Metabolic acidosis increases intracellular calcium in bone cells through activation of the proton receptor OGR1

J Bone Miner Res. 2009 Feb;24(2):305-13. doi: 10.1359/jbmr.081015.

Abstract

Metabolic acidosis increases urine Ca without increasing intestinal absorption, leading to bone Ca loss. It is unclear how bone cells detect the increase in proton concentration. To determine which G protein-coupled proton sensing receptors are expressed in bone, PCR was performed, and products were detected for OGR1, TDAG8, G2A, and GPR4. We tested the hypothesis that the G protein-coupled proton sensor, OGR1, is an H(+)-sensing receptor in bone. To determine whether acid-induced bone resorption involves OGR1, we incubated mouse calvariae in neutral pH (NTL) or acidic (MET) medium +/- the OGR1 inhibitor CuCl(2). CuCl(2) decreased MET-induced Ca efflux. We used fluorescent imaging of perfused bone cells to determine whether MET increases Ca(i). Perfusion with MET induced a rapid, flow-independent, increase in Ca(i) in individual bone cells. To determine whether transfection of OGR1 into a heterologous cell type would increase Ca(i) in response to H(+), we perfused Chinese hamster ovary (CHO) cells transfected with mouse OGR1 cDNA. Perfusion with MET induced a rapid increase in Ca(i) in OGR1-transfected CHO cells. These data indicate that OGR1 induces an increase in Ca(i) in response to MET and is a prime candidate for an osteoblast proton sensor.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acidosis / metabolism*
  • Animals
  • Bone Resorption / metabolism
  • Bone and Bones / cytology*
  • Bone and Bones / drug effects
  • Bone and Bones / metabolism*
  • CHO Cells
  • Calcium / metabolism*
  • Copper / pharmacology
  • Cricetinae
  • Cricetulus
  • Intracellular Space / drug effects
  • Intracellular Space / metabolism*
  • Mice
  • Protons
  • Receptors, G-Protein-Coupled / metabolism*
  • Transfection

Substances

  • GPR68 protein, mouse
  • Protons
  • Receptors, G-Protein-Coupled
  • Copper
  • cupric chloride
  • Calcium