Cooperation of Two Subtypes of PGE<sub>2</sub> Receptor, Gi Coupled EP3 and Gs Coupled EP2 or EP4 Subtype

DOI Web Site Web Site PubMed 48 References
  • HATAE Noriyuki
    <i>Department of Physiological Chemistry, Graduate School of Pharmaceutical Sciences, Kyoto University</i>

Bibliographic Information

Other Title
  • 複数のプロスタグランジンE<sub>2</sub>受容体サブタイプを介する相乗的なcAMP産生機構
  • 複数のプロスタグランジンE2受容体サブタイプを介する相乗的なcAMP産生機構
  • フクスウ ノ プロスタグランジン E2 ジュヨウタイ サブタイプ オ カイスル ソウジョウテキ ナ cAMP サンセイ キコウ

Search this article

Abstract

Four prostaglandin E (EP) receptor subtypes have been identified and cloned, designated as EP1, EP2, EP3 and EP4. These EP receptors are members of the G-protein coupled receptor family. EP3 receptor signals are primarily involved in inhibition of adenylyl cyclase via Gi activation, while EP2 and EP4 receptor signals cause a stimulation of adenylyl cyclase via Gs activation. Immune cells, such as mast cells, express multiple EP subtypes on their cell membranes, but few studies have been conducted to understand exactly what signals the main flow for the multiple subtypes expressing immune cells. We previously demonstrated that activation of Gi-coupled EP3 receptor exhibited a cooperative effect on cAMP synthesis induced by Gs-coupled EP2 receptor in COS-7 cells. Here we report that a selective EP4 agonist-induced adenylyl cyclase activity was augmented by simultaneous addition of a selective EP3 agonist in mastocytoma P-815 cells, which express mRNAs for both EP3 and EP4 subtypes. The augmentation in cAMP synthesis was found to be pertussis toxin-sensitive. P-815 cells are demonstrated to bind to Pronectin-F, a proteolytic fragment of fibronectin, in adhesion protein of the extracellular matrix, by addition of PGE2, which is mediated by PKA. The binding of P-815 cells to Pronectin-F mediated by EP4 receptor was augmented by the EP3 receptor. These findings indicate that two subtypes of PGE2 receptors, EP3 and EP4, cooperatively activate the cAMP-mediated adhesion event through induction of fibronectin ligand elicited by PGE2 in P-815 cells. Furthermore, the PGE2-induced adhesion response may contribute to the mast cell recruitment function on extracellular matrix during inflammation.<br>

Journal

  • YAKUGAKU ZASSHI

    YAKUGAKU ZASSHI 123 (10), 837-843, 2003-10-01

    The Pharmaceutical Society of Japan

References(48)*help

See more

Keywords

Details 詳細情報について

Report a problem

Back to top