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Query: UNIPROT:P01178 (oxytocin)
 15,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In previous work we reported that oxytocin activates phospholipase-C (PLC) and increases prostaglandin E2 (PGE2) release in amnion. Whether either of the consequences of activation of PLC by oxytocin, activation of protein kinase-C (PKC) or increases in intracellular calcium, directly results in the production of PGE2 is unknown. Phorbol esters (PMA) and epidermal growth factor (EGF) are also known to increase PGE2 release from amnion. In some tissues these agents are capable of activating the PLC postreceptor cascade system. This study was undertaken primarily to explore the mechanism of oxytocin-induced PGE2 production in amnion and secondarily to determine whether common aspects of PGE2 production by oxytocin, PMA, and EGF include activation of PLC or subsequent steps in this cascade followed by new mRNA/protein production. Involvement of PLC was assessed by inositol phosphate (IP1) turnover. IP1 turnover was increased by oxytocin (2.99 +/- 0.31-fold; P less than 0.01), but not by EGF or PMA. PMA inhibited oxytocin-provoked IP1 turnover (P less than 0.05). PKC involvement was initially evaluated with two PKC inhibitors, H7 and staurosporine. Each inhibited PGE2 production by oxytocin as well as that by PMA and EGF in a dose-dependent fashion. With H7, the IC50 for all agents was 5 microM; the IC50 for staurosporine was 2 nM for PMA and oxytocin and 5 nM for EGF. Agonist-induced PGE2 production was also assessed in cells in which PKC activity had been tachyphylaxed with a high concentration of PMA (400 ng/mL for 48 h). In such cells oxytocin and PMA no longer stimulated (P less than 0.001) PGE2 production, but EGF-stimulated PGE2 production was only slightly reduced. PKC involvement is, thus, implicated for oxytocin and PMA. Other enzymes that are inhibited by H7 and staurosporine are implicated in the production of PGE2 caused by EGF. Although tachyphylaxed cells produced no PGE2 with oxytocin, oxytocin increased intracellular calcium to levels higher than those seen in control cells (435 +/- 102 vs. 286 +/- 1.2) Actinomycin-D (P less than 0.001) and cycloheximide (P less than 0.05) inhibited PGE2 production caused by oxytocin, PMA, and EGF. PGE2 production by oxytocin in human amnion cells proceeds by activation of PKC, followed by new protein and mRNA production. Further, in cells without PKC, oxytocin-induced calcium transients do not increase PGE2. The ability of EGF to stimulate PGE2 in cells with no PKC activity also establishes that PKC activation is not a common intracellular step in the induction of PGE2 production by all agents.
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PMID:Protein kinase-C activation is required for oxytocin-induced prostaglandin production in human amnion cells. 202 8

Oxytocin (OT)-stimulated PGE2 release by rabbit amnion is enhanced by the up-regulation of oxytocin receptors (OTR), which increase about 200-fold at the end of pregnancy. As recent studies have shown that PGs are essential for parturition, the rise in amnion OTR and associated PGE2 synthesis are probably essential for labor initiation. The present work was directed toward understanding the mechanisms of OTR up-regulation. Levels of agents that stimulate adenylyl cyclase activity and cortisol are increased in amniotic fluid at the end of pregnancy. Addition of either forskolin or cortisol to cultured amnion cells caused an increase in OTR ligand-binding sites and steady state OTR messenger RNA (mRNA) levels. Forskolin treatment elevated OTR mRNA levels rapidly, but transiently, whereas cortisol's effects were slower and sustained. Actinomycin or cycloheximide, added 3 h after forskolin, led to a sustained elevation in OTR mRNA levels, suggesting that forskolin increases the activities of OTR mRNA-destabilizing factors along with increasing OTR mRNA concentration. Cortisol did not appear to affect OTR mRNA stability. Measurement of OTR mRNA transcription rates showed that forskolin's effects were maximal within 1 h of treatment. In contrast, cortisol-induced transcription was not apparent until 8 h. The effects of forskolin and cortisol on OTR gene transcription were synergistic. Thus, the increase in OTR mRNA levels occurring after either forskolin or cortisol treatments is the result of induction of OTR gene expression, but the effects of the two agents appear to occur at separate sites.
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PMID:Induction of oxytocin receptor gene expression in rabbit amnion cells. 968 95

The effects of cycloheximide and actinomycin on 8-bromo-cAMP (8-Br-cAMP) stimulated vasopressin and oxytocin release from the posterior pituitary and vasopressin mRNA content of the supraoptic nucleus were studied with perifused explants of the hypothalamo-neurohypophyseal system. 8-Br-cAMP stimulated vasopressin and oxytocin release from the explant for up to 6 h. Inhibition of protein synthesis by cycloheximide completely suppressed the response to 8-Br-cAMP. When gene transcription was inhibited by actinomycin, vasopressin release was stimulated by 8-Br-cAMP for approximately 2 h, but the response was not sustained. Vasopressin mRNA content was not changed by 8-Br-cAMP in the absence or presence of cycloheximide, but it was significantly decreased by simultaneous exposure to 8-Br-cAMP and actinomycin. Actinomycin alone did not change vasopressin mRNA content. Since other studies have demonstrated that cAMP stimulates vasopressin gene transcription, and since vasopressin mRNA content reflects the balance between gene transcription and mRNA degradation, the effect of actinomycin and 8-Br-cAMP on vasopressin mRNA content suggests that 8-Br-cAMP also decreased vasopressin mRNA stability and thereby induced a rapid turnover of vasopressin mRNA. The effects of cycloheximide and actinomycin on vasopressin and oxytocin release suggest that ongoing protein synthesis is required for stimulation of hormone release. Since the posterior pituitary hormone stores are not depleted with a stimulus for release that is even more potent than cAMP, it is possible that cycloheximide and actinomycin depleted smaller pools of the peptides such as those responsible for intranuclear vasopressin and oxytocin release. Further evidence that intranuclear release of vasopressin and oxytocin is a prerequisite for cAMP stimulation of vasopressin and oxytocin release was obtained by demonstrating that d(CH2)5-D-Tyr(Me)VAVP, a potent combined V1a/V2/oxytocin receptor antagonist blocked stimulation of vasopressin and oxytocin release by 8-Br-cAMP.
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PMID:cAMP stimulation of vasopressin and oxytocin release and regulation of vasopressin mRNA stability: role of auto-facilitation. 1116 41