Prostaglandin EP3 receptor superactivates adenylyl cyclase via the Gq/PLC/Ca2+ pathway in a lipid raft-dependent manner

Kumiko Yamaoka, Akiko Yano, Kenji Kuroiwa, Kazushi Morimoto, Tomoaki Inazumi, Noriyuki Hatae, Hiroyuki Tabata, Eri Segi-Nishida, Satoshi Tanaka, Atsushi Ichikawa, Yukihiko Sugimoto

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

We previously demonstrated that prostaglandin EP3 receptor augments EP2-elicited cAMP formation in COS-7 cells in a Gi/o-insensitive manner. The purpose of our current study was to identify the signaling pathways involved in EP3-induced augmentation of receptor-stimulated cAMP formation. The enhancing effect of EP3 receptor was irrespective of the C-terminal structure of the EP3 isoform. This EP3 action was abolished by treatment with inhibitors for phospholipase C and intracellular Ca2+-related signaling molecules such as U73122, staurosporine, 2-APB and SK&F 96365. Indeed, an EP3 agonist stimulated IP3 formation and intracellular Ca2+ mobilization, which was blocked by U73122, but not by pertussis toxin. The enhancing effect by EP3 on cAMP formation was mimicked by both a Ca2+ ionophore and the activation of a typical Gq-coupled receptor. Moreover, EP3 was exclusively localized to the raft fraction in COS-7 cells and EP3-elicited augmentation of cAMP formation was abolished by cholesterol depletion and introduction of a dominant negative caveolin-1 mutant. These results suggest that EP3 elicits adenylyl cyclase superactivation via Gq/phospholipase C activation and intracellular Ca2+ mobilization in a lipid raft microdomain-dependent manner.

Original languageEnglish
Pages (from-to)678-682
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume389
Issue number4
DOIs
Publication statusPublished - Nov 27 2009
Externally publishedYes

Fingerprint

Prostaglandin Receptors
COS Cells
Type C Phospholipases
Programmable logic controllers
Adenylyl Cyclases
Prostaglandins
Chemical activation
Cyclic AMP Receptors
Lipids
Caveolin 1
Staurosporine
Ionophores
Pertussis Toxin
Protein Isoforms
Cholesterol
Molecules
1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione

Keywords

  • Caveolin
  • GPCR
  • Prostanoid
  • Raft
  • Signal cross-talk

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Molecular Biology

Cite this

Prostaglandin EP3 receptor superactivates adenylyl cyclase via the Gq/PLC/Ca2+ pathway in a lipid raft-dependent manner. / Yamaoka, Kumiko; Yano, Akiko; Kuroiwa, Kenji; Morimoto, Kazushi; Inazumi, Tomoaki; Hatae, Noriyuki; Tabata, Hiroyuki; Segi-Nishida, Eri; Tanaka, Satoshi; Ichikawa, Atsushi; Sugimoto, Yukihiko.

In: Biochemical and Biophysical Research Communications, Vol. 389, No. 4, 27.11.2009, p. 678-682.

Research output: Contribution to journalArticle

Yamaoka, K, Yano, A, Kuroiwa, K, Morimoto, K, Inazumi, T, Hatae, N, Tabata, H, Segi-Nishida, E, Tanaka, S, Ichikawa, A & Sugimoto, Y 2009, 'Prostaglandin EP3 receptor superactivates adenylyl cyclase via the Gq/PLC/Ca2+ pathway in a lipid raft-dependent manner', Biochemical and Biophysical Research Communications, vol. 389, no. 4, pp. 678-682. https://doi.org/10.1016/j.bbrc.2009.09.064
Yamaoka, Kumiko ; Yano, Akiko ; Kuroiwa, Kenji ; Morimoto, Kazushi ; Inazumi, Tomoaki ; Hatae, Noriyuki ; Tabata, Hiroyuki ; Segi-Nishida, Eri ; Tanaka, Satoshi ; Ichikawa, Atsushi ; Sugimoto, Yukihiko. / Prostaglandin EP3 receptor superactivates adenylyl cyclase via the Gq/PLC/Ca2+ pathway in a lipid raft-dependent manner. In: Biochemical and Biophysical Research Communications. 2009 ; Vol. 389, No. 4. pp. 678-682.
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