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

Keywords

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

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    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, 389(4), 678-682. https://doi.org/10.1016/j.bbrc.2009.09.064