Isolated rat stomach ECL cells generate prostaglandin E 2 in response to interleukin-1β, tumor necrosis factor-α and bradykinin

Abstract

The ECL cells control parietal cells by releasing histamine in their immediate vicinity. Gastrin and pituitary adenylate cyclase-activating peptide (PACAP) stimulate histamine secretion from isolated ECL cells, while somatostatin and galanin inhibit stimulated secretion. Prostaglandin E 2 and related prostaglandins likewise suppress ECL-cell histamine secretion. Conceivably, that is how they inhibit acid secretion. In the present study, we examined if prostaglandin E 2 can be generated by isolated ECL cells. Rat stomach ECL cells were purified (>90% purity) by counterflow elutriation and gradient centrifugation and cultured for 48 h. ECL cell stimulants (gastrin and PACAP) and inflammatory agents (interleukin-1β, tumor necrosis factor-α and bradykinin) were tested for their ability to induce prostaglandin E 2 accumulation (24-h incubation), measured by radioimmunoassay. Gastrin and PACAP did not affect prostaglandin E 2 accumulation but interleukin-1β (300 pg/ml), tumor necrosis factor-α (10 ng/ml) and bradykinin (1 μM) induced a 2- to 3-fold increase in the amount of prostaglandin E 2 accumulated. While the combination of interleukin-1β and bradykinin induced a 9-fold increase, the combination interleukin-1β+tumor necrosis factor-α and bradykinin+tumor necrosis factor-α induced additive effects only. The combination of interleukin-1β+tumor necrosis factor-α+bradykinin did not induce a greater effect than interleukin-1β+bradykinin. The effect of interleukin-1β+bradykinin was abolished by adding 10 nM hydrocortisone (suppressing phospholipase A 2 and cyclooxygenase) or 1 μM indomethacin (inhibiting cyclooxygenase). Incubating ECL cells in the presence of interleukin-1β+bradykinin for 24 h reduced their ability to secrete histamine in response to gastrin. The inhibitory effect was reversed by 1 μM indomethacin. Also, increasing the concentrations of hydrocortisone in the medium resulted in an enhanced gastrin-stimulated histamine secretion. Hence, the previously described acid-inhibiting effect of inflammatory agents may be explained by inhibition of ECL-cell histamine mobilization, consequent to enhanced formation of prostaglandin E 2 by cells in the oxyntic mucosa, including the ECL cells themselves.