Induction of adherent activity in mastocytoma P-815 cells by the cooperation of two prostaglandin E2 receptor subtypes, EP3 and EP4

Noriyuki Hatae, Ayumi Kita, Satoshi Tanaka, Yukihiko Sugimoto, Atsushi Ichikawa

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21 Citations (Scopus)


In this study, we investigated the role of PGE2 in mouse mastocytoma P-815 cell adhesion to extracellular matrix proteins (ECMs) in vitro. We report that PGE2 accelerated ProNectin F™ (a proteolytic fragment of fibronectin)-mediated adhesion, which was abolished by addition of the GRGDS peptide, an inhibitor of the RDG binding site of ProNectin F™. We show that the cAMP level and cAMP-regulated protein kinase (PKA) activity are critical mediators of this PGE2 effect, because the cell-permeable cAMP analogue 8-Br-cAMP accelerated P-815 cell adhesion to ProNectin F™ and the pharmacological inhibitor of PKA, H-89, blocked PGE2-mediated adhesion. Consistent with mRNA expression of the Gscoupled EP4- and Gi-coupled EP3-PGE receptor subtypes, P-815 cell adhesion was accelerated by treatment with a selective EP4 agonist, ONO-AE1-329, but not a selective EP1/EP3 agonist, sulprostone. However, simultaneous treatment with ONO-AE1-329 and sulprostone resulted in augmentation of both the cAMP level and cell adhesion. The augmentation of EP3-mediated cAMP synthesis was dose-dependent, without affecting the half-maximal concentration for EP4-mediated Gs-activity, which was inhibited by a Gi inhibitor, pertussis toxin. In conclusion, these findings suggest that PGE2 accelerates RGD-dependent adhesion via cooperative activation between EP3 and EP4 and contributes to the recruitment of mast cells to the ECM during inflammation.

Original languageEnglish
Pages (from-to)17977-17981
Number of pages5
JournalJournal of Biological Chemistry
Issue number20
Publication statusPublished - May 16 2003

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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