title: ERK2 mediates oxytocin-stimulated PGE2 synthesis.
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 Gi and Gq/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 p42MAPK), which was partially inhibited by pertussis toxin (PTX), consistent with OTR-Gi coupling. The PTX-insensitive portion of ERK2 phosphorylation was linked to Gq, 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.
authors.affiliation: Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston 77555-1062, USA.
authors.forename: Z
authors.initials: Z
authors.lastname: Strakova
authors.forename: J A
authors.initials: JA
authors.lastname: Copland
authors.forename: S J
authors.initials: SJ
authors.lastname: Lolait
authors.forename: M S
authors.initials: MS
authors.lastname: Soloff
mesh_terms: D000818:Animals; D016466:CHO Cells; D002118:Calcium / Q000494:pharmacology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000502:physiology*; D006224:Cricetinae; D015232:Dinoprostone / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000378:metabolism; D048369:MAP Kinase Kinase 1; D048370:MAP Kinase Kinase 2; D019950:Mitogen-Activated Protein Kinase 1; D020929:Mitogen-Activated Protein Kinase Kinases; D010121:Oxytocin / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D011493:Protein Kinase C / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics; D012333:RNA, Messenger / Q000037:antagonists & inhibitors; D051381:Rats; D018045:Receptors, Oxytocin / Q000378:metabolism; D013936:Thymidine / Q000493:pharmacokinetics; D014158:Transcription, Genetic / Q000187:drug effects; D010738:Type C Phospholipases / Q000502:physiology
chemical_list: D004791:Enzyme Inhibitors; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D018045:Receptors, Oxytocin; D010121:Oxytocin; D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; D011493:Protein Kinase C; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048369:MAP Kinase Kinase 1; D048370:MAP Kinase Kinase 2; D020929:Mitogen-Activated Protein Kinase Kinases; D010738:Type C Phospholipases; D019204:GTP-Binding Proteins; D015232:Dinoprostone; D002118:Calcium; D013936:Thymidine