Involvement of lipoxygenase products in myometrial contractions

Carraher, Robert P.; Hahn, Do Won; Ritchie, David M.; McGuire, J.L.

doi:10.1016/0090-6980(83)90071-0

Cited by 70 publications

(20 citation statements)

References 10 publications

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“…Leukotrienes have been postulated to increase the sensitivity to pain in the uterus [1,4,13,14,41] and to cause uterine contractions [15]. Indeed, higher circulating levels of LTC 4 and LTD 4 have been found in the menstrual blood of women with primary dysmenorrhea [13,14] and thus, the inhibition of uterine contraction via a reduction of these cysteinyl-leukotrienes represents a plausible molecular mechanism for the BNO 1095 action, as observed in the rat in vivo experiments.…”

Section: Reduction Of Pro-inflammatory Signaling Molecules By Bno 1095mentioning

confidence: 97%

“…Leukotrienes are synthesized from arachidonic acid involving 5-LO and represent important lipid mediators of the inflammatory immune response that are known to accompany menstruation [13,15,41]. We therefore investigated the effect of the extract on 5-LO product biosynthesis in a cell-free (purified enzyme) and cellbased (in human monocytes) model.…”

Section: Bno 1095 Did Not Substantially Inhibit Purified Phosphodiestmentioning

confidence: 99%

“…Also 10-30 % of dysmenorrheic women are not responsive to COX inhibitors [13], suggesting the role of other mediators in this condition. For example, an elevation of leukotrienes observed in women with primary dysmenorrhea has been suggested to contribute to uterine hypercontraction in humans [14] and as shown in a guinea pig experimental model [15]. However, no medicinal products acting on the 5-lipoxygenase pathway have been approved for treatment of PMS so far.…”

Section: Introductionmentioning

confidence: 99%

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Vitex agnus-castus dry extract BNO 1095 (Agnucaston®) inhibits uterine hyper-contractions and inflammation in experimental models for primary dysmenorrhea

et al. 2016

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Background: For many women, the monthly suffering induced by menstrual "cramps" is severe enough to profoundly disrupt their quality of life. In the case of primary dysmenorrhea, a condition related to premenstrual syndrome (PMS), intense uterine contractions are thought to trigger moderate to intense pain despite the absence of an underlying infection or other medically-identifiable disease states. The associated uterine hyper-contractility is reminiscent of labor, and associated pain is likely to be mediated by the release of prostaglandins, leukotrienes and the infiltration of leukocytes that normally accompany the breakdown of the endometrial lining. Standardized extracts of Vitex agnus-castus berries (VAC extracts of chaste tree, or chaste berries) are clinically effective in treating the symptoms of PMS, yet the mechanisms of how the chemically complex mixture acts are largely unknown. Methods: Using an in vivo dysmenorrhea model rats were treated with 10 mg/kg estradiol-benzoate i.p. once daily for 12 days and with 2.1, 10.3 or 20.7 mg/kg VAC dry extract p.o. once daily for 7 days prior to induction of convulsions. Uterine contractions where induced with 2 IU/kg oxytocin i.p., followed by monitoring of abdominal convulsions and signs of pain on the last day of the experiment. Moreover, in vitro methods were applied that are described in the methods section. Results: Here, we show that the VAC herbal dry extract BNO 1095 (commercially available as Agnucaston

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Section: Reduction Of Pro-inflammatory Signaling Molecules By Bno 1095mentioning

confidence: 97%

Section: Bno 1095 Did Not Substantially Inhibit Purified Phosphodiestmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Vitex agnus-castus dry extract BNO 1095 (Agnucaston®) inhibits uterine hyper-contractions and inflammation in experimental models for primary dysmenorrhea

et al. 2016

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“…The glucocorticoid-infused, chronically prepared ovine fetal model has proved successful for the investigation of new tocolytic therapies (Poore et al 1999). PGs, specifically PGF 2 , mediate myometrial contractions associated with the onset of labour in both sheep and humans (Carraher et al 1983, Wiqvist et al 1983. Further understanding of the specific regulation of intrauterine PG synthesis may provide a rational basis for the development of new and effective tocolytic therapies.…”

Section: Introductionmentioning

confidence: 99%

Changes in the expression of prostaglandin E and F synthases at induced and spontaneous labour onset in the sheep

Palliser¹,

Gt²,

Hirst³

et al. 2004

Journal of Endocrinology

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The differential production of prostaglandin (PG) F 2 and PGE 2 within the uterine compartment may play a role in controlling myometrial contraction. We hypothesized that the enzymes downstream of PG endoperoxide synthase-2 (PGHS-2) determine the ratio of PGF 2 and PGE 2 in the utero-ovarian vein plasma and the time of normal and preterm labour onset. The aim of this study was to simultaneously determine the expression of PGF and PGE synthases (PGFS and PGES) in gestational tissues at spontaneous and induced-preterm labour in sheep. Myometrial, endometrial and placental tissue were obtained from ewes in dexamethasone-induced preterm labour, age-matched control ewes, and ewes in spontaneous term labour for analysis of mRNA expression by real-time PCR. PGFS mRNA expression was significantly increased following dexamethasone-induced and spontaneous labour onset in placentome (P,0·01) but was unchanged in the myometrium and endometrium. In contrast, PGES mRNA expression remained unchanged or decreased. PGHS-2 mRNA expression was increased in all tissues examined in both dexamethasone-induced and spontaneous labour (P,0·001). Plasma PGE 2 and PGF 2 concentrations rose in both dexamethasoneinduced and spontaneous labour with the ratio of PGF 2 :PGE 2 increased with labour onset (P,0·05). These results are consistent with the hypothesis that the increased expression, of PGFS is responsible for the increased PGF 2 :PGE 2 ratio and this, together with increased PGHS-2 expression, accounts for myometrial activity at labour onset. The findings point to PGFS expression as a key factor in regulating the uterotonic process in the sheep.

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“…There is good evidence for prostaglandins, in particular PGE 2 and PGF 2 , being important mediators in the onset of human labour by inducing myometrial contractions (Carraher et al 1983), ripening of the cervix (Ellwood et al 1980) and membrane rupture (Challis & Olson 1988). Prostaglandins are produced by the amnion, chorion, decidua, myometrium and placenta (Duchesne et al 1978).…”

Section: Introductionmentioning

confidence: 99%

Regulation of prostaglandin production in intact fetal membranes by interleukin-1 and its receptor antagonist

Brown

Alvi²,

Elder³

et al. 1998

Journal of Endocrinology

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There is strong evidence for the involvement of inflammatory mediators such as interleukin (IL)-1 in the biochemical mechanisms of parturition. Therefore the effects of the IL-1 family (IL-1 (1 ng/ml), IL-1 (1 ng/ ml) and the IL-1 receptor antagonist (IL-1ra) (10 ng/ml)) on the regulation of prostaglandin synthesis in term human fetal membranes were investigated. It was found that, after 4 h of culture, IL-1 increased prostaglandin E 2 (PGE 2 ) output approximately twofold. This was associated with both a significant increase in cyclo-oxygenase-2 (COX-2) mRNA levels (approximately fourfold compared with control) and translocation of cytoplasmic phospholipase A 2 (cPLA 2 ) from the cytosol to the membrane fraction. IL-1 was less effective than IL-1 at stimulating PGE 2 production through similar mechanisms.IL-1ra had no effect on PGE 2 output. However, in combination treatments, IL-1ra did not inhibit IL-1 -or IL-1 -stimulated PGE 2 output, and increased PGE 2 production further compared with IL-1 alone. IL-1ra decreased IL-1 -induced COX-2 mRNA expression by about half and significantly increased cPLA 2 protein levels, as detected by immunoblotting, when used alone and together with IL-1 . These results suggest that IL-1ra has partial agonist properties when used together with IL-1 and IL-1 in fetal membranes by increasing cPLA 2 protein levels, which leads to an increase in the production of prostaglandins.

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Involvement of lipoxygenase products in myometrial contractions

Cited by 70 publications

References 10 publications

Vitex agnus-castus dry extract BNO 1095 (Agnucaston®) inhibits uterine hyper-contractions and inflammation in experimental models for primary dysmenorrhea

Vitex agnus-castus dry extract BNO 1095 (Agnucaston®) inhibits uterine hyper-contractions and inflammation in experimental models for primary dysmenorrhea

Changes in the expression of prostaglandin E and F synthases at induced and spontaneous labour onset in the sheep

Regulation of prostaglandin production in intact fetal membranes by interleukin-1 and its receptor antagonist

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