Erk-2 mediates oxytocin-stimulated pge2 synthesis.
Strakova, Zuzana, John A. Copland, Stephen J. Lolait, Melvyn S.
Soloff.
Department of Obstetrics and Gynecology, University of Texas
Medical Branch, Galveston TX 77555-1062. Laboratory of Cellular and
Molecular Regulation, National Institute of Mental Health, Bethesda,
MD 20892. Sealy Center for Molecular Science, University of Texas
Medical Branch, Galveston TX 77555-1062
APStracts 4:0281E, 1997.
Oxytocin (OT) induces prostaglandin 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 ERK-2
(p42MAPK), which was partially inhibited by pertussis toxin (PTX),
consistent with OTR/Gi coupling. The PTX-insensitive portion of ERK-2
phosphorylation was linked to Gq, as inhibitors of both PLC (U73122)
and PKC (GF 109203X) blocked OT-induced ERK-2 phosphorylation. OT
-stimulated c-fos expression was also mediated by ERK-2
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 ERK-2 phosphorylation with an ERK kinase inhibitor (PD98059)
markedly reduced OT-stimulated PGE2 synthesis, pointing to the
importance of ERK-2 activation in OT action.
Received 1 October 1997; accepted in final form 12 December 1997.
APS Manuscript Number E461-7.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 7 January 1998