The principal function of the bicarbonate concentration (HCOminus) of saliva is to buffer changes in the pH of the oral cavity. HCOminus is secreted by the acinar cells of the salivary glands into the lumen through the chloride channel which is under the control of cyclic nucleotides and cytoplasmic calcium. Thus I conclude that salivary buffer capacity is in part directly regulated by the concentration of secondary messengers in the cytoplasm of acinar cells. In this application, I shall show that there is a tight, inverse relationship between pHi and cytoplasmic calcium. The working hypothesis is that cytoplasmic hydrogen ions (i.e., pHi) inhibit calcium influx during activation. This hypothesis predicts that the efflux HCOminus from the parotid cell is a self-limiting phenomenon (i.e., negative feedback regulation involving 2 cytoplasmic ions--calcium and hydrogen). My preliminary evidence shows that cytoplasmic calcium is influenced by pHi in a directly varying relationship. There is also evidence that the Na+/Ca++ exchange and calcium pump of the surface membrane is sensitive to pHi. If this hypothesis could be proven, then this would establish how acinar cells secreted HCOminus without jeopardizing their own capacity to buffer the decrease in pHi that occasions cellular activation. Also this research would give us clues s to the nature of the mechanism responsible for the influx of calcium during activation which is a point of major controversy. The experiments in this application will: 1) establish the relationship between pHi and cytoplasmic calcium in precise, quantitative terms and 2) characterize the pHi-sensitive transporters of calcium ions. This information is essential to establish a foundation for investigating the presence of negative-feedback regulation that controls acinar cell physiology.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
5R01DE010602-03
Application #
2015122
Study Section
Oral Biology and Medicine Subcommittee 1 (OBM)
Project Start
1994-09-30
Project End
1998-09-29
Budget Start
1996-09-30
Budget End
1998-09-29
Support Year
3
Fiscal Year
1996
Total Cost
Indirect Cost
Name
University of the Pacific-San Francisco
Department
Type
Schools of Dentistry
DUNS #
City
San Francisco
State
CA
Country
United States
Zip Code
94115