ERK2 mediates oxytocin-stimulated PGE2 synthesis

Zuzana Strakova, John A III Copland, Stephen J. Lolait, Melvyn S. Soloff

65 Scopus citations

Abstract

Oxytocin (OT) induces PG synthesis by both uterine endometrial and amnion cells. We showed previously that CHO cells stably transfected with the rat oxytocin receptor (CHO-OTR cells) also synthesize PGE2 in response to OT. In the present work we have demonstrated that OTRs are coupled to both G(i) and G(q/11), using immunoprecipitation of solubilized OTR complexes and ADP ribosylation. OT treatment caused the rapid phosphorylation of extracellular signal-regulated protein kinase 2 (ERK2 or p42(MAPK)), which was partially inhibited by pertussis toxin (PTX), consistent with OTR-G(i) coupling. The PTX-insensitive portion of ERK2 phosphorylation was linked to G(q), as inhibitors of both phospholipase C (U-73122) and protein kinase C (GF-109203X) blocked OT-induced ERK2 phosphorylation. OT-stimulated c-fos expression was also mediated by ERK2 phosphorylation. The ERK-c-fos pathway has been shown to be associated with cell proliferation, but OT had no effect on [3H]thymidine uptake by CHO-OTR cells. However, inhibition of OT-induced ERK2 phosphorylation with an ERK kinase inhibitor (PD-98059) markedly reduced OT-stimulated PGE2 synthesis, pointing to the importance of ERK2 activation in OT action.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume274
Issue number4 37-4
StatePublished - Apr 1998
Externally publishedYes

Keywords

  • G proteins
  • Mitogen-activated protein kinase
  • Oxytocin receptor
  • Prostaglandin E2
  • Protein kinase C

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Physiology
  • Physiology (medical)

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