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

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

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
Volume278
Issue number20
DOIs
Publication statusPublished - May 16 2003
Externally publishedYes

Fingerprint

Receptors, Prostaglandin E, EP3 Subtype
Receptors, Prostaglandin E, EP4 Subtype
Mastocytoma
Dinoprostone
Cell adhesion
Cell Adhesion
Military electronic countermeasures
Adhesion
glycyl-arginyl-glycyl-aspartyl-serine
Extracellular Matrix Proteins
Pertussis Toxin
Protein Kinase Inhibitors
Fibronectins
Mast Cells
Protein Kinases
Chemical activation
Binding Sites
Pharmacology
Inflammation
Messenger RNA

ASJC Scopus subject areas

  • Biochemistry

Cite this

Induction of adherent activity in mastocytoma P-815 cells by the cooperation of two prostaglandin E2 receptor subtypes, EP3 and EP4. / Hatae, Noriyuki; Kita, Ayumi; Tanaka, Satoshi; Sugimoto, Yukihiko; Ichikawa, Atsushi.

In: Journal of Biological Chemistry, Vol. 278, No. 20, 16.05.2003, p. 17977-17981.

Research output: Contribution to journalArticle

Hatae, Noriyuki ; Kita, Ayumi ; Tanaka, Satoshi ; Sugimoto, Yukihiko ; Ichikawa, Atsushi. / Induction of adherent activity in mastocytoma P-815 cells by the cooperation of two prostaglandin E2 receptor subtypes, EP3 and EP4. In: Journal of Biological Chemistry. 2003 ; Vol. 278, No. 20. pp. 17977-17981.
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