REGULATION OF PLATELET-ACTIVATING-FACTOR PRODUCTION IN GASTRIC EPITHELIAL-CELLS

The authors have previously reported that platelet-activating factor ( PAF), a phospholipid mediator with potent proinflammatory activities, is produced in the gastric mucosa and stimulates gastric acid secretio n in humans and animals. In the present study they used the human gast ric tumour cells HGT1 (clone 6) to examine whether PAF production is r egulated by neuromediators. PAF was extracted by ethanol and assayed b y the washed platelet aggregation test. HGT1 cells produced PAF sponta neously (110 +/- 20 pg 10(6) cells). The addition of vasoactive intest inal peptide (VIP; 10(-9) to 10(-7) mol L(-1)) or of histamine (10(-5) to 10(-3) mol L(-1)) increased PAF production by three- to fivefold, while the addition of carbachol (10(-7) to 10(-4) mol L(-1)) increased PAF production up to sevenfold. PAF production was also increased up to 10- to 13-fold, in a dose- and time-dependent manner, by the additi on of calcium and two- to threefold by the addition of phorbol myrista te acetate (PMA; 10(-7) to 10(-5) mol L(-1)). However, the addition of dibutyryl cyclic AMP (dBcAMP; 10(-6) to 10(-4) mol L(-1)) was without any effect. This is the first report showing PAF production by gastri c epithelial cells in response to histamine, VIP and carbachol. Furthe rmore, the findings are consistent with a central role of calcium in t his production. The results of this study, together with those of prev ious studies from the authors' laboratory, support the hypothesis that PAF is a physiological mediator of gastric acid secretion.