Pregnancy increases ET-1-induced contraction and changes receptor subtypes in uterine smooth muscle in humans

Osada, Kayo; Tsunoda, Hajime; Miyauchi, Takashi; Sugishita, Yasuro; Kubo, Takeshi; Goto, Katsutoshi

doi:10.1152/ajpregu.1997.272.2.r541

Cited by 18 publications

(16 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…It could be postulated that the counteractive effect of progesterone to estrogen during the luteal phase creates conditions of contractility in the myometrium similar to those in postmenopausal women, but this requires investigation. The intracellular mechanism that could mediate the enhanced responsiveness of estrogendeprived human uterus may be associated with alterations in the receptor's functions leading to changes in the post-receptor biochemical events (Osada et al 1997).…”

Section: Tablementioning

confidence: 99%

“…It has been demonstrated that in human nonpregnant myometrium, ET1 induces contractions , Fried et al 1993, Svane et al 1993 activating exclusively the ETA receptors, and increasing the two phases of spontaneous myometrial contractility, the phasic and the tonic phase, despite the lesser sensitivity of nonpregnant compared with pregnant myometrium (Word et al 1991, Osada et al 1997. Although binding studies have shown that ET1 exhibits affinity for ETB receptors, activation of ETB sites, using ETB selective ligands, has not been reported to mediate any contractile effect on human myometrial tissue; the lack of any contractile effect on human nonpregnant uterus has been attributed to the small population of ETB receptors (less than 25%) on human myometrium, or to their involvement in mechanisms of relaxation and proliferation; the precise role of ETB subtypes of receptors in human uterus needs to be further elucidated (Maggi et al 1994, Bacon et al 1995, Heluy et al 1995, Wolff et al 1996, Osada et al 1997. However, in none of these studies has the effect of ET1 on myometrial contractility been examined specifically in relation to the hormonal profile of the women.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

In vitro effects of endothelin-1 on the contractility of myometrium obtained from pre- and postmenopausal women

Domali¹,

Asprodini²,

Molyvdas³

et al. 2001

Journal of Endocrinology

View full text Add to dashboard Cite

This study was conducted to evaluate the responsiveness of human nonpregnant myometrium to endothelin 1 (ET1) (10 10 M-10 6 M) and KCl (80 mM) in relation to the hormonal profile of the women, who were allocated into three groups: group 1, premenopausal follicular phase, n=14, group 2, premenopausal luteal phase, n=20, and group 3, postmenopausal women, n=12. At a concentration of 10 6 M, ET1 in both groups 1 and 2 induced very low ripples of high frequency (group 1: 80 14%, n=5, group 2: 314 63%, n=11; P<0·05 compared with the pretreatment frequency) which lasted significantly longer in group 2 (29 2 min, n=10, P<0·05) than in group 1 (20 2 min, n=5), increasing the basal tone (group 1: 57·9 6%, n=5, group 2: 64·4 4%, n=6), the amplitude of myometrial contractility (group 1: 1·2 0·07 g, n=5, group 2: 1·6 0·1 g, n=7, P<0·05) and the area under the contractility curve (AUC; group 1: 8·4 1·1 g min, n=6, group 2: 11·9 1·6 g min, n=11). In group 3, ET1 (10 6 M) created a sustained long-lasting contraction (initial phase: 43 6 min, n=6) characterized by the complete obliteration of spontaneous contractility with no ripples at all, and increasing significantly (P<0·05) the amplitude of myometrial contractility (2·8 0·5 g, n=6), the AUC (24·7 3·3 g min, n=6), as well as the basal tone (183·6 21%, n=6) compared with the two premenopausal groups. In all three groups KCl exposure induced an initial rise (mean amplitude value: 1·1 g) followed by a relaxation phase to the primal baseline level (mean duration value: 12 min). Addition of ET1 (10 6 M) to KCl (80 mM) induced a similar pattern of contractility to that evoked by ET1 alone which, compared with KCl alone lasted significantly longer (P<0·05) in all three groups (group 1: 20 2 min, n=6; group 2: 23 2 min, n=6; group 3: 35 3 min, n=5). In group 3, the percentage change in basal tone was significantly smaller following KCl than after the combination of KCl plus ET1 (149 16%, n=5; P<0·01), indicating a different mechanism of contractility between KCl and ET1. These results demonstrate for the first time differences in myometrial response to ET1 between pre-and postmenopausal women. It is suggested that KCl and ET1 affect uterine contractility through different mechanisms and that ovarian steroids may play a regulatory role in human uterine responsiveness to ET1.

show abstract

Section: Tablementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

In vitro effects of endothelin-1 on the contractility of myometrium obtained from pre- and postmenopausal women

Domali¹,

Asprodini²,

Molyvdas³

et al. 2001

Journal of Endocrinology

View full text Add to dashboard Cite

show abstract

“…The concentration of ET-1 in maternal blood is increased during pregnancy and reaches a peak at term [3], and its concentration in amniotic fluid is also high [4]. Human uterine muscle is sensitive to ET-1 [5], and ET-1-induced uterine contraction is markedly increased at the end of pregnancy [6]. In addition, rat uterine contractile responsiveness to ET-1 is elevated during labor and diminished postpartum.…”

Section: Introductionmentioning

confidence: 99%

“…Taken together, these data suggest a role for ET-1 in the initiation and maintenance of labor. Two types of endothelin-receptors, ET A and ET B , coexist in human myometrial tissues, but only the proportion of ET A receptor is increased in the pregnant myometrium [6][7][8]. The myometrial ET A receptor is linked to a membrane phosphoinositide-specific phospholipase C [8,9].…”

Section: Introductionmentioning

confidence: 99%

Selective Protein Kinase C Isoforms Are Involved in Endothelin-1-Induced Human Uterine Contraction at the End of Pregnancy

Eude

Paris

Cabrol

et al. 2000

Biology of Reproduction

View full text Add to dashboard Cite

The role of protein kinase C (PKC) in contraction of the human myometrium induced by endothelin-1 (ET-1) was investigated at the end of pregnancy. The expression and subcellular distribution of PKC isoforms were examined by Western blot analysis using isoform-specific antibodies. At least three conventional PKC isoforms (cPKC; alpha, beta1, and beta2), two novel PKC isoforms (epsilon and delta), and an atypical PKC isoform (zeta) were detected in pregnant myometrium. Quantitative immunoblotting revealed that all these isoforms were mainly distributed in the particulate fraction. The lack of a calcium chelator to modify the particulate sequestration of cPKC suggests an interaction with an anchoring protein such as receptor-activated C kinase-1, which is evidenced in the particulate fraction of the pregnant myometrium. Of the six isoforms, only PKCbeta1, PKCbeta2, PKCdelta, and PKCzeta were translocated to the particulate fraction, and PKCepsilon to the cytoskeletal fraction, after stimulation with ET-1. Involvement of PKC in the ET-1-induced contractile response is supported by the inhibition caused by the PKC inhibitor calphostin C. However, we demonstrated that the selective cPKC isoform inhibitor, Gö 6976, as well as the substantial depletion of PKCbeta1 and PKCepsilon and the partial depletion of PKCalpha and PKCdelta by a long-term treatment with phorbol 12,13-dibutyrate did not prevent ET-1-induced contraction. Accordingly, our results suggest that PKCdelta and PKCzeta activation mediated ET-1-induced contraction, whereas cPKC isoforms were not implicated in the human pregnant myometrium.

show abstract

“…Endothelin-1 maternal plazmada ve amniyon sıvısında gebelik süresince giderek artar (7,8). Endotelin uterus ve plasental yataktaki damarların düz kas hücrelerinin kasılmasını sağlar (9)(10)(11)(12) …”

Section: Introductionunclassified

Normal ve Sezeyan Doğumlarda Maternal ve Umbinikal Kordon Karnında Endotelin-1 Düzeyleri

Baytur¹,

Ulman²,

Tama³

et al. 2004

Ankara Sa

View full text Add to dashboard Cite

ÖZETAmaç: Spontan vajinal doğumlar ve sezeryan doğumlarda maternal ve umbilikal kordon kanında endotelin-1 düzeyini ölçmek.Gereç ve Yöntem: 2003 yılında hastanemize doğum yapmak üzere başvuran toplam 37 kadından doğum sırasında maternal ve umbilikal kordon kanı alındı. Hipertansif, preeklamptik, erken membran rüptürü olan, diyabetik, kalp hastası kadınlar çalışma dışı bırakıldı. 37. haftadan önce doğum yapmış kadınlar preterm, 37 hafta ve sonrasında doğum yapmışlar term kabul edildi. Sezeryan olan kadınların hiçbiri ameliyat öncesi travay çekmedi. Normal term (n=17), preterm (n=4) ve sezeryan (n=16) doğumlarda maternal ve umbilikal kordon kanı endotelin-1 düzeyleri karşılaştırıldı.İstatistikler SPSS 10.0 programında, Kruskal-Wallis varyans ve Mann-Whitney U testleri kullanılarak yapıldı. P<0,05 istatistiksel olarak anlamlı kabul edildi.Bulgular: Normal term doğumlarda, maternal ve umbilikal kord kan endotelin-1 düzeyleri sezeryan doğumlara göre daha fazlaydı, fakat bu fark istatistiksel olarak anlamlı düzeyde değildi. (Maternal kanda 1.37 ± 0,69'a karşı 1.11 ± 0,3, umbilikal kord kanında 3.9 ± 1.8'e karşı 3.7 ± 2.4 pg/ml) (p>0,05). Preterm doğumlarda ise maternal kanda endotelin-1 düzeyi, normal doğumlardan az, sezeryanlardan ise fazla idi (1,15 ± 0,24).Sonuç: Term ya da preterm normal doğum grubunda, kan endotelin-1 düzeylerinin, travay çekmemiş sezeryan grubundan daha fazla olması, endotelin-1'in doğum ağrılarının başlamasında rol oynadığını düşündürmektedir.Anahtar Kelimeler: Endotelin-1, vajinal doğum, sezeryan, preterm doğum. SUMMARY:Aim: To measured endothelin-1 levels of maternal and umbilical cord blood plasma in normal spontaneous vaginal delivery and cesarean sections.Material and Methods: Maternal and umbilical cord blood plasma were taken from 37 pregnant women who admitted to our hospital during year 2003 for delivery to measure endothelin-1 levels. Women who have hypertension, preeclampsia, heart disease, diabetes were excluded from study. Women who delivered before 37 weeks of gestation were accepted as preterm and women who delivered in or after 37 weeks of gestation were accepted as term. None of the women in cesarean group had labour before operation. Normal vaginal term (n=17), preterm (n=4) and cesarean (n=16) delivery groups were compared for maternal and umbilical cord blood plasma endothelin-1 levels. Statistical analysis were performed in SPSS for windows version 10.0 using Kruskal-Wallis variance and Mann-Whitney U test. P<0,05 was considered statisticaly significant.Results: Maternal and umbilical cord blood plasma endothelin-1 levels were higher in normal vaginal delivery group, when compared to cesarean group, although it didn't reach statisticaly significant level (1.37 ± 0,69 versus 1,11 ± 0,3 pg/ml in maternal blood, 3.9 ± 1,8 versus 3,7 ± 2,4 pg/ml in umbilical

show abstract

Pregnancy increases ET-1-induced contraction and changes receptor subtypes in uterine smooth muscle in humans

Cited by 18 publications

References 0 publications

In vitro effects of endothelin-1 on the contractility of myometrium obtained from pre- and postmenopausal women

In vitro effects of endothelin-1 on the contractility of myometrium obtained from pre- and postmenopausal women

Selective Protein Kinase C Isoforms Are Involved in Endothelin-1-Induced Human Uterine Contraction at the End of Pregnancy

Normal ve Sezeyan Doğumlarda Maternal ve Umbinikal Kordon Karnında Endotelin-1 Düzeyleri

Contact Info

Product

Resources

About