Extracellular Ca(2+) sensing in salivary ductal cells

J Biol Chem. 2012 Aug 31;287(36):30305-16. doi: 10.1074/jbc.M112.394122. Epub 2012 Jul 9.

Abstract

Ca(2+) is secreted from the salivary acinar cells as an ionic constituent of primary saliva. Ions such as Na(+) and Cl(-) get reabsorbed whereas primary saliva flows through the salivary ductal system. Although earlier studies have shown that salivary [Ca(2+)] decreases as it flows down the ductal tree into the oral cavity, ductal reabsorption of Ca(2+) remains enigmatic. Here we report a potential role for the G protein-coupled receptor, calcium-sensing receptor (CSR), in the regulation of Ca(2+) reabsorption by salivary gland ducts. Our data show that CSR is present in the apical region of ductal cells where it is co-localized with transient receptor potential canonical 3 (TRPC3). CSR is activated in isolated salivary gland ducts as well as a ductal cell line (SMIE) by altering extracellular [Ca(2+)] or by aromatic amino acid, L-phenylalanine (L-Phe, endogenous component of saliva), as well as neomycin. CSR activation leads to Ca(2+) influx that, in polarized cells grown on a filter support, is initiated in the luminal region. We show that TRPC3 contributes to Ca(2+) entry triggered by CSR activation. Further, stimulation of CSR in SMIE cells enhances the CSR-TRPC3 association as well as surface expression of TRPC3. Together our findings suggest that CSR could serve as a Ca(2+) sensor in the luminal membrane of salivary gland ducts and regulate reabsorption of [Ca(2+)] from the saliva via TRPC3, thus contributing to maintenance of salivary [Ca(2+)]. CSR could therefore be a potentially important protective mechanism against formation of salivary gland stones (sialolithiasis) and infection (sialoadenitis).

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Biological Transport / genetics
  • Calcium / metabolism*
  • Cell Line
  • Male
  • Mice
  • Receptors, Calcium-Sensing / genetics
  • Receptors, Calcium-Sensing / metabolism*
  • Salivary Duct Calculi / genetics
  • Salivary Duct Calculi / metabolism*
  • Salivary Duct Calculi / pathology
  • Salivary Ducts / metabolism*
  • Salivary Ducts / pathology
  • TRPC Cation Channels / genetics
  • TRPC Cation Channels / metabolism*

Substances

  • Receptors, Calcium-Sensing
  • TRPC Cation Channels
  • TRPC3 cation channel
  • Calcium