Abstract
This study was undertaken to further understanding of the mechanisms which regulate acid secretion by isolated parietal cells. The particular aims of this work were to investigate the sites at which calcium-sensitive and phospholipid-dependent protein kinase, protein kinase C, could act to modulate acid secretion, and to establish the site, and mechanism by which epidermal growth factor(EGF) inhibits acid secretion. The intracellular accumulation of the weak base aminopyrine was used as an index of parietal cell secretory activity.Experiments using 12-0-tetradecanoylphorbol-13 acetate (TPA) and 1-oleoyl-2-acetylglycerol (OAG) to activate protein kinase C suggested three sites of action of this enzyme. TPA dose-dependently inhibited the histamine plus 3-isobutyl-1-methylxanthine ( IBMX)stimulated increase in cellular cyclic AMP implicating a site of action at, or close to, adenylate cyclase. A site of action distal to adenylate cyclase was also suggested since TPA was an effective inhibitor of aminopyrine accumulation in cells stimulated by dibutyryl cyclic AMP. TPA and OAG transiently increased the aminopyrine accumulation ratio in cells incubated in a medium containing 100mM-K+. This effect of TPA and OAG did not involve histamine, acetylcholine or changes in cellular cyclic AMP levels. It is therefore possible that a stimulatory site of action of protein kinase C exists within these cells.
Activators of protein kinase C inhibited secretory activity under conditions where EGF was ineffective. Although EGF stimulated the production of prostaglandin E2 by a parietal cell-enriched preparation under basal conditions, there was no effect with histamine present. EGF dose-dependently inhibited the histamine-induced increase in the aminopyrine accumulation ratio and cyclic AMP content. This effect was blocked by IBMX, and it is therefore possible that the antisecretory effect of EGF was due to an increase in cyclic AMP phosphodiesterase activity.
Date of Award | Nov 1988 |
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Original language | English |
Awarding Institution |
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Keywords
- Regulation
- acid secretion
- Pacieral cells
- rat
- stomach