Role of intracellular Ca2+ and the calmodulin messenger system in pepsinogen secretion from isolated rabbit gastric mucosa

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Abstract

Both carbachol (10-4-10-3 mol/1) and cholecystokinin octapeptide (CCK-8) (10-8-10-6 mol/1) significantly stimulated the release of pepsinogen from rabbit gastric mucosa maintained in organ culture (213-216% and 143-261% of control, respectively, p<0·05-0·01). The secretion was not affected by removing Ca2+ from the culture medium with ethylene glycol tetra-acetic acid. Verapamil failed to inhibit the secretion of pepsinogen induced by the drugs in ordinary culture medium containing Ca2+. In contrast, nicorandil (10-6-10-4 mol/l) attenuated the release of pepsinogen by the drugs in a dose dependent manner, regardless of the presence or absence of Ca2+ in the culture medium. W-7 (10-6-10-4 mol/l) and W-5 (10-5 and 10-4, or 10-6 mol/l) reduced significantly the secretion of pepsinogen induced by carbachol (53-71% and 63-81% of control, respectively, p<0·05-0·01) and that by CCK-8 (49-67% and 66-76% of control, respectively, p<0·01) in the Ca2+ containing medium. However, W-7 did not show significant inhibition of cyclic adenosine monophosphate (cAMP) and forskolin induced pepsinogen secretion. These findings indicate that the calmodulin messenger branch that is activated by a rise of intracellular Ca2+ mobilised in cytosol from its intracellular, but not extracellular, source plays a critical role in pepsinogen secretion induced by carbachol and CCK-8. It seems likely that an increase in cAMP in cytosol does not provoke any calmodulin mediated pepsinogen secretion. present in eukaryotes, forms an active complex with Ca2+, activating enzymes and culminating in physiological cell responses.4 5 The role of this messenger branch has been partially defined in pancreatic islet β cells, blood platelets, and smooth muscle,4 but its part in the secretion of pepsinogen by the gastric chief cells has not been fully investigated. We have therefore assessed the role of the calmodulin pathway in the calcium dependent secretion of pepsinogen using calmodulin antagonists.

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Miyamoto, T., Itoh, M., Noguchi, Y., & Yokochi, K. (1992). Role of intracellular Ca2+ and the calmodulin messenger system in pepsinogen secretion from isolated rabbit gastric mucosa. Gut, 33(1), 21–25. https://doi.org/10.1136/gut.33.1.21

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