Type 2 lysophosphatidic acid receptor in gastric surface mucous cells: Possible implication of prostaglandin E2 production.

Lysophosphatidic acid (LPA) is a lipid mediator that induces various cell responses via its specific receptors. Recently, we found that orally administered LPA and phosphatidic acid (PA) ameliorate stress- or aspirin-induced stomach injury. However, the mechanisms underlying these effects have not been elucidated yet. In this study, we examined effect of LPA on prostaglandin (PG) E2 production in MKN74 cells, a gastric cell-line expressing type 2 LPA receptor (LPA2). When the cells were treated with LPA, the level of mRNA of COX-2 but not COX-1 was upregulated. The LPA effect was abolished when the cells were pretreated with pertussis toxin (PTX), suggesting the involvement of receptor(s) coupled with Gi. Pretreatment of MKN74 cells with LPA enhanced the PGE2 production triggered by calcium ionophore A23187. Again, PTX abolished the LPA effect. Fluorescent immunohistochemistry using an antibody against LPA2 showed that surface mucous cells (pit cells) in gastric mucosa of mice express LPA2 on the apical side of the plasma membrane. These results suggest that LPA in the diet or its digestion may contribute to the epithelial integrity of stomach mucosa by enhancement of PGE2 production via activation of LPA2.