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

The ECL cells control parietal cells by releasing histamine in their immedi ate vicinity. Gastrin and pituitary adenylate cyclase-activating peptide (P ACAP) stimulate histamine secretion from isolated ECL cells, while somatost atin and galanin inhibit stimulated secretion. Prostaglandin E-2 and relate d prostaglandins likewise suppress ECL-cell histamine secretion. Conceivabl y, that is how they inhibit acid secretion. In the present study, we examin ed if prostaglandin E-2 can be generated by isolated ECL cells. Rat stomach ECL cells were purified (> 90% purity) by counterflow elutriation and grad ient centrifugation and cultured for 48 h. ECL cell stimulants (gastrin and PACAP) and inflammatory agents (interleukin-1 beta, tumor necrosis factor- alpha 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-1 b eta (300 pg/ml), tumor necrosis factor-alpha (10 ng/ml) and bradykinin (1 m uM) induced a 2- to 3-fold increase in the amount of prostaglandin E-2 accu mulated. While the combination of interleukin-1 beta and bradykinin induced a 9-fold increase, the combination interleukin-1 beta + tumor necrosis fac tor-alpha and bradykinin + tumor necrosis factor-alpha induced additive eff ects only. The combination of interleukin-1 beta + tumor necrosis factor-al pha + bradykinin did not induce a greater effect than interleukin-1 beta bradykinin. The effect of interleukin-1 beta + bradykinin was abolished by adding 10 nM hydrocortisone (suppressing phospholipase A(2) and cyclooxygen ase) or 1 muM indomethacin (inhibiting cyclooxygenase). Incubating ECL cell s in the presence of interleukin-1 beta + bradykinin for 24 h reduced their ability to secrete histamine in response to gastrin. The inhibitory effect was reversed by 1 muM indomethacin. Also, increasing the concentrations of hydrocortisone in the medium resulted in an enhanced gastrin-stimulated hi stamine secretion. Hence, the previously described acid-inhibiting effect o f inflammatory agents may be explained by inhibition of ECL-cell histamine mobilization, consequent to enhanced formation of prostaglandin E-2 by cell s in the oxyntic mucosa, including the ECL cells themselves. (C) 2001 Elsev ier Science B.V. All rights reserved.