Extracellular Ca(2+) sensing in salivary ductal cells.
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).
Calcium Signaling Laboratory, Research Service, Veterans Affairs Medical Center, Washington, DC 20422, USA. bidhan.bandyopadhyay@va.gov
Bidhan C
BC
Bandyopadhyay
William D
WD
Swaim
Ankana
A
Sarkar
Xibao
X
Liu
Indu S
IS
Ambudkar
D000818:Animals; D001692:Biological Transport / Q000235:genetics; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D008297:Male; D051379:Mice; D044169:Receptors, Calcium-Sensing / Q000235:genetics / Q000378:metabolism*; D012465:Salivary Duct Calculi / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018987:Salivary Ducts / Q000378:metabolism* / Q000473:pathology; D050052:TRPC Cation Channels / Q000235:genetics / Q000378:metabolism*
D044169:Receptors, Calcium-Sensing; D050052:TRPC Cation Channels; C104603:TRPC3 cation channel; D002118:Calcium