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Cellular distribution of gastric chief cell protein kinase C activity: Differential effects of diacylglycerol, phorbol esters, carbachol, and cholecystokinin
Author(s) -
Raffaniello Robert D.,
Raufman JeanPiean
Publication year - 1992
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.240480115
Subject(s) - diacylglycerol kinase , protein kinase c , carbachol , secretion , cholecystokinin , endocrinology , gastric chief cell , medicine , chemistry , biology , stimulation , biochemistry , phosphorylation , gastric mucosa , receptor , stomach
Stimulation of chief cells with carbachol or cholecystokinin (CCK) results in the production of inositol trisphosphate (IP 3 ) and diacylglycerol (DAG). Although IP 3 increases cell calcium concentration, thereby stimulating pepsinogen secretion, the role of DAG and its target, protein kinase C (PKC), is less clear. To examine the relation between the cellular distribution of PKC activity and pepsinogen secretion, we determined PKC activity in cytosolic and membrane fractions from dispersed chief cells from guinea pig stomach. To validate our assay, we studied the actions of the phorbol ester PMA. PMA caused a rapid, dose‐dependent, 6‐fold increase in pepsinogen secretion and membrane‐associated PKC activity. Similarly, dose‐response curves for pepsinogen secretion and the increase in membrane‐associated PKC activity induced by a membrane‐permeant DAG (1‐oleoyl‐2‐acetylglycerol) were superimposable. In contrast, CCK (0.1 nM to 1.0 μM) and carbachol (0.1 μM to 1.0 mM) caused a 4‐fold increase in pepsinogen secretion, but did not alter the distribution of PKC activity. These results indicate that in gastric chief cells, PMA‐and DAG‐induced pepsinogen secretion is accompanied by increased membrane‐associated PKC activity. However, the cellular distribution of PKC activity is not altered by CCK or carbachol.