Calcium, Calmodulin, and Cycle Adenosine Monophosphate Modulate Prostaglandin E2Release from Isolated Human Gastric Mucosal Cells*

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Abstract
We studied prostaglandin E2 (PGE2) releasefrom isolated cells of the human gastric mucosa. Mucosal cellswere enzymaticajly isolated from biopsy specimens of humanfundic mucosa. The results from these crude cell preparationswere compared to those obtained in fractions with enriched (65-80%) or depleted parietal cell content (3-7%) which were preparedfrom gastric mucosa obtained at surgery. PGE2 release inthe enriched parietal cell fractions exceeded that from crude orparietal cell depleted preparations 3- and 13-fold, respectively.However, despite this quantitative difference, all preparationsresponded similarly to the test agents. Newly synthesized PGE2was not stored intracellularly but was released into the incubationmedium. Release increased linearly for 30 min. Addition ofthe calcium ionophore A23187 enhanced PGE2 release 4- to 5-fold. The effect of A23187 required the presence of extracellular Ca2+ (10-3 mol/liter). Assuming that A23187 alters Ca2+ flux ingastric cells as it does in other cell systems our data indicatethat increased Ca2+ influx enhances PGE2 release. Since calmodulinis of importance for intracellular Ca2+ action, the calmodulinantagonists trifluoperazine and W7 were tested. Bothantagonists inhibited PGE2 release by 65-85%, trifluoperazinebeing slightly more effective. Activation of the adenylate cyclasesystem by forskolin or direct addition of (Bu)2cAMP, a stablecAMP-analog, also inhibited PGE2 release. We conclude thatPGE2 is released from parietal and from nonparietal cells of thehuman gastric mucosa, although the major quantity is releasedfrom the light density fraction that is enriched in parietal cells.In parietal and nonparietal cells Ca2+ is of importance in theregulation of gastric mucosal PGE2 release and calmodulin seemsto mediate this intracellular action of Ca2+. cAMP inhibits PGE2-release from gastric cells.