Z. Strakova et al., ERK2 MEDIATES OXYTOCIN-STIMULATED PGE(2) SYNTHESIS, American journal of physiology: endocrinology and metabolism, 37(4), 1998, pp. 634-641
Oxytocin (OT) induces PCT synthesis by both uterine endometrial and am
nion cells. We showed previously that CHO cells stably transfected wit
h the rat oxytocin receptor (CHO-OTR cells) also synthesize PGE(2) 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 solubi
lized OTR complexes and ADP ribosylation. OT treatment caused the rapi
d 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 o
f ERK2 phosphorylation was linked to G(q), as inhibitors of both phosp
holipase C (U-73122) and protein kinase C (GF-109203X) blocked OT-indu
ced ERK2 phosphorylation. OT-stimulated c-fos expression was also medi
ated by ERK2 phosphorylation. The ERK-c-fos pathway has been shown to
be associated with cell proliferation, but OT had no effect on [H-3]th
ymidine uptake by CHO-OTR cells. However, inhibition of OT-induced ERK
2 phosphorylation with an ERK kinase inhibitor (PD-98059) markedly red
uced OT-stimulated PGE(2) synthesis, pointing to the importance of ERK
2 activation in OT action.