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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Kaufhold, Marc Rieg, Timo Seidler, Ursula Fährmann, Michael |
| Description | Author Affiliation: Fährmann M ( Institut für Zoophysiologie der Westfälischen Wilhelms-Universität Münster, Hindenburgplatz 55, D-48143 Münster, Germany. fahrman@uni-muenster.de) |
| Abstract | 1. The phorbol ester TPA, an activator of protein kinase C (PKC), inhibits cholinergic stimulation of gastric acid secretion but increases basal H(+) secretion. 2. Since these contradictory findings suggest the action of different PKC isozymes we analysed the role of calcium-dependent PKC-alpha, and calcium-independent PKC-epsilon in gastric acid secretion. 3. Inhibition of PKC-alpha by the indolocarbazole Gö 6976 revealed that about 28% of carbachol-induced acid secretion was inhibited by PKC-alpha. In the presence of Gö 6976 approximately 64% of the carbachol-induced signal transduction is mediated by Ca(2+)/calmodulin-dependent protein kinase II (CaMKII), and 14% is conveyed by PKC-epsilon as deduced from the inhibition with the bisindolylmaleimide Ro 31-8220. 4. Inhibition of carbachol-induced acid secretion by TPA was accompanied by a decrease in CaMKII activity. 5. The stimulation of basal acid secretion by TPA was biphasic with a peak at a very low concentration (10 pM), resulting in an activation of the calcium-sensor CaMKII. The activation was determined with a phosphospecific polyclonal antibody against active CaMKII. The TPA-induced increase of H(+) secretion was sensitive to the cell-permeable Ca(2+)-chelator BAPTA/AM, Ro 31-8220, and the CaMKII-inhibitor KN-62, but not to Gö 6976. 6. Since TPA induced the translocation of PKC-epsilon but not of PKC-alpha in resting parietal cells, PKC-epsilon seems to be at least responsible for an initial elevation of free intracellular calcium to initiate TPA-induced acid secretion. 7. Our data indicate the different roles of two PKC isoforms: PKC-epsilon activation appears to facilitate cholinergic stimulation of H(+)-secretion likely by increasing intracellular calcium. In contrast, PKC-alpha activation attenuates acid secretion accompanied by a down-regulation of CaMKII activity. |
| ISSN | 00071188 |
| e-ISSN | 14765381 |
| Journal | British Journal of Pharmacology |
| Issue Number | 6 |
| Volume Number | 136 |
| Language | English |
| Publisher | Wiley Online Library(on behalf of The British Pharmacological Society) |
| Publisher Date | 2002-07-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | Open |
| Subject Keyword | Gastric Acid Secretion Protein Kinase C Metabolism Animals Blotting, Western Calcium-Calmodulin-Dependent Protein Kinase Type 2 Calcium-Calmodulin-Dependent Protein Kinases Antagonists & Inhibitors Carbachol Pharmacology Carbazoles Cells, Cultured Enzyme Activators In Vitro Techniques Indoles Parietal Cells, Gastric Drug Effects Enzymology Protein Kinase C-alpha Protein Kinase C-epsilon Rabbits Tetradecanoylphorbol Acetate |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology |
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