Abstract

The major goal of this work is to determine how the acid-secreting parietal cells of the rabbit stomach maintain ionic homeostasis during large changes in their secretory activity. Microspectrofluorimetry and digital image processing of pH-, Na- Ca-, Cl- and K-sensitive fluorescent dyes will be used to determine how the ion exchangers (Na/H, Cl/HCO3, and Na/Ca), cotransporter (Na/HCO3), ATP-ases (Na/K and H/K), and Ca """"""""channels"""""""" are controlled by the H2 agonist histamine and muscarinic agonist carbachol. The roles which different second messengers like Ca, pH, CAMP and protein kinase C may play in stimulus secretion coupling will also be investigated, as will the roles which Na/H and Cl/HC03 exchange might play in maintenance of the """"""""barrier"""""""" function of the enzyme-secreting chief cells and mucus-secreting surface epithelial cells. These data will be of importance in knowing how stomach cells operate in healthy and diseased states. Also, since the membrane transport processes and stimulus-secretion coupling mechanisms are present in most secretory cells, the work should have quite broad relevance.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK019520-13
Application #
3226423
Study Section
Physiology Study Section (PHY)
Project Start
1977-04-01
Project End
1994-11-30
Budget Start
1990-12-20
Budget End
1991-11-30
Support Year
13
Fiscal Year
1991
Total Cost
Indirect Cost

  Institution

Name
University of California Berkeley
Department
Type
Schools of Arts and Sciences
DUNS #
094878337
City
Berkeley
State
CA
Country
United States
Zip Code
94704

  Publications

Bischof, G; Serwold, T F; Machen, T E (1997) Does nitric oxide regulate capacitative Ca influx in HEK 293 cells? Cell Calcium 21:135-42
Sammak, P J; Hinman, L E; Tran, P O et al. (1997) How do injured cells communicate with the surviving cell monolayer? J Cell Sci 110 ( Pt 4):465-75
Hofer, A M; Curci, S; Machen, T E et al. (1996) ATP regulates calcium leak from agonist-sensitive internal calcium stores. FASEB J 10:302-8
Illek, B; Fischer, H; Machen, T E (1996) Alternate stimulation of apical CFTR by genistein in epithelia. Am J Physiol 270:C265-75
Hofer, A M; Schlue, W R; Curci, S et al. (1995) Spatial distribution and quantitation of free luminal [Ca] within the InsP3-sensitive internal store of individual BHK-21 cells: ion dependence of InsP3-induced Ca release and reloading. FASEB J 9:788-98
Negulescu, P A; Machen, T E (1995) La3+ and pH sensitivity of Ca2+ entry and intracellular store filling in gastric parietal cells. Am J Physiol 269:G770-8
Illek, B; Fischer, H; Santos, G F et al. (1995) cAMP-independent activation of CFTR Cl channels by the tyrosine kinase inhibitor genistein. Am J Physiol 268:C886-93
Bischof, G; Brenman, J; Bredt, D S et al. (1995) Possible regulation of capacitative Ca2+ entry into colonic epithelial cells by NO and cGMP. Cell Calcium 17:250-62
Bischof, G; Illek, B; Reenstra, W W et al. (1995) Role for tyrosine kinases in carbachol-regulated Ca entry into colonic epithelial cells. Am J Physiol 268:C154-61
Poulsen, J H; Fischer, H; Illek, B et al. (1994) Bicarbonate conductance and pH regulatory capability of cystic fibrosis transmembrane conductance regulator. Proc Natl Acad Sci U S A 91:5340-4

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