Oxytocin stimulates mitogen-activated protein kinase activity in cultured human puerperal uterine myometrial cells.

Abstract

The regulation of mitogen-activated protein (MAP) kinase by oxytocin in cultured human uterine myometrial cells was investigated. Oxytocin caused the rapid stimulation of MAP kinase activity detected in 32P incorporation of MAP-2. Oxytocin also stimulated the phosphorylation of MAP kinase detected in incorporation of [32P]orthophosphate into MAP kinase. Furthermore, oxytocin induced the tyrosine phosphorylation of MAP kinase. The oxytocin-dependent increase in the tyrosine phosphorylation of MAP kinase displayed a transient time course and was dependent on the concentration of oxytocin applied to the cells. Furthermore, we examined the mechanism by which oxytocin induced MAP kinase phosphorylation. Islet-activating protein (100 ng/ml), which inactivates Gi/Go proteins, blocked the oxytocin-induced phosphorylation of MAP kinase. Moreover, 1 microM ritodrine, which is known to relax uterine muscle contraction, attenuated oxytocin-induced MAP kinase activity and phosphorylation. These results provide evidence that oxytocin acutely activates MAP kinase through an islet-activating protein-sensitive G-protein in human uterine myometrial cells, suggesting that this new pathway may play an important role in the biological action of oxytocin on these cells.

Localization of the human oxytocin receptor in caveolin-1 enriched domains turns the receptor-mediated inhibition of cell growth into a proliferative response

“…It is interesting to note that this PAR2 mutant showed the same defective internalization and desensitization as the OTR-GFP-cav2 mutant described here. Since human OTR activates the p42/44 and p38 MAPK pathways via both sensitive and insensitive PTX signalling pathways (Hoare et al, 1999;Ohmichi et al, 1995;Strakova et al, 1998), it can be hypothesized that OTR localized in caveolar domains activate the MAP kinase in a Ras-dependent pathway leading to the activation and translocation of ERK1/ERK2 and cell proliferation, whereas the inhibition of cell growth may be associated with PLC-and PCK-dependent and Ras-independent activation. Experiments using inhibitors of the dierent signalling pathways potentially involved in MAPK activation by OTR-GFP-cav2 or WT OTR-GFP are currently under way in order to test this hypothesis.…”

The Comprehensive Neural Mechanism of Oxytocin in Analgesia

“…In addition to its well-known functions, such as strengthening uterine contractions during childbirth and promoting lactation, the role of OXT in analgesia has also received increasing attention [ 27 ]. OXT can upregulate the activity of 5'-adenosine monophosphate (AMP) activated protein kinase (AMPK) mediated by G protein [ 28 ]. After combining with OXTR, OXT can activate protein kinase C (PKC), phospholipase C (PLC), and other systems and trigger a series of biological events by increasing the concentration of endogenous Ca 2+ [ 29 ].…”

Investigation of metal modulation of oxytocin structure receptor-mediated signaling

“…14–17 In particular, many of these functions are associated with activation of the ERK1/2 MAPK pathway. 18–22…”

“…[14][15][16][17] In particular, many of these functions are associated with activation of the ERK1/2 MAPK pathway. [18][19][20][21][22] To this end, we hypothesize that Zn(II) and Cu(II) play differential roles in modulating and directing OT towards the various signaling pathways that it can activate, and that a closer investigation of the molecular components that govern OT/ metal interactions is warranted. In this work, we assess the impact of Zn(II) and Cu(II) on peptide secondary structure under biologically relevant conditions not only with native oxytocin, but in both cyclic and linear analogs where potential binding regions are perturbed (Fig.…”