Uterine Quiescence: The Role of Cyclic AMP

Price, Sarah; Bernal, Andrés López

doi:10.1113/eph8602182

Cited by 47 publications

(30 citation statements)

References 39 publications

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“…Activated currents exhibited outward rectification in physiological K ϩ , modest rectification in symmetrical K ϩ , timedependent activation at more positive membrane potentials, a lack of inactivation, and a flickering appearance. These properties are consistent with those previously reported for TREK-1 (45,48,56,60) and channels in mouse myometrium (55). These data illustrate the functional presence of TREK-1 K ϩ channels and currents in smooth muscle cells isolated from pregnant human myometrium.…”

Section: Discussionsupporting

confidence: 81%

“…Ovariectomized mice also demonstrated a decrease in TREK-1 expression compared with wild-type mice (55). Interestingly, TREK-1 expression was reduced in full-term and preterm laboring vs. nonlaboring human myometrium (13), consistent with the notion that TREK-1 contributes to myometrial quiescence during gestation.…”

Section: Discussionsupporting

confidence: 71%

“…In addition to factors that could alter the activity of TREK-1 channels already discussed, recently published data show that the expression of TREK-1 protein is higher in pregnant than nonpregnant myometrium in human (13) and mouse (55). Ovariectomized mice also demonstrated a decrease in TREK-1 expression compared with wild-type mice (55).…”

Section: Discussionmentioning

confidence: 98%

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TREK-1 currents in smooth muscle cells from pregnant human myometrium

Heyman

Cowles

Barnett

et al. 2013

American Journal of Physiology-Cell Physiology

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The mechanisms governing maintenance of quiescence during pregnancy remain largely unknown. The current study characterizes a stretch-activated, tetraethylammoniuminsensitive K ϩ current in smooth muscle cells isolated from pregnant human myometrium. This study hypothesizes that these K ϩ currents can be attributed to TREK-1 and that upregulation of this channel during pregnancy assists with the maintenance of a negative cell membrane potential, conceivably contributing to uterine quiescence until full term. The results of this study demonstrate that, in pregnant human myometrial cells, outward currents at 80 mV increased from 4.8 Ϯ 1.5 to 19.4 Ϯ 7.5 pA/pF and from 3.0 Ϯ 0.8 to 11.8 Ϯ 2.7 pA/pF with application of arachidonic acid (AA) and NaHCO 3, respectively, causing intracellular acidification. Similarly, outward currents were inhibited following application of 10 M fluphenazine by 51.2 Ϯ 9.8% after activation by AA and by 73.9 Ϯ 4.2% after activation by NaHCO3. In human embryonic kidney (HEK-293) cells stably expressing TREK-1, outward currents at 80 mV increased from 91.0 Ϯ 23.8 to 247.5 Ϯ 73.3 pA/pF and from 34.8 Ϯ 8.9 to 218.6 Ϯ 45.0 pA/pF with application of AA and NaHCO3, respectively. Correspondingly, outward currents were inhibited 89.5 Ϯ 2.3% by 10 M fluphenazine following activation by AA and by 91.6 Ϯ 3.4% following activation by NaHCO3. Moreover, currents in human myometrial cells were activated by stretch and were reduced by transfection with small interfering RNA or extracellular acidification. Understanding gestational regulation of expression and gating of TREK-1 channels could be important in determining appropriate maintenance of uterine quiescence during pregnancy.

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Section: Discussionsupporting

confidence: 81%

Section: Discussionsupporting

confidence: 71%

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TREK-1 currents in smooth muscle cells from pregnant human myometrium

Heyman

Cowles

Barnett

et al. 2013

American Journal of Physiology-Cell Physiology

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“…The onset of labour in women could be due to loss of uterine quiescence, the induction of uterine contractility or a combination of both (Price & Lopez Bernal 2001, Ló pez Bernal 2003. Multiple related pathways have been studied: one of the pathways involves corticotrophin-releasing hormone (CRH; McLean et al 1995).…”

Section: Introductionmentioning

confidence: 99%

Low abundance plasma proteins in labour

Wang¹,

Heesom²,

Phillips³

et al. 2012

Reproduction

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Every year, millions of births worldwide are complicated by prematurity or difficult post-term deliveries, resulting in a high incidence of perinatal mortality and morbidity. Our poor understanding of human parturition is a key reason for our inability to improve the management of preterm and post-term birth. In this study, we used proteomic techniques to look into protein changes in placental blood plasma obtained from women before or after spontaneous or induced labour, with vaginal or caesarean section deliveries. Our aim was to understand the basic mechanisms of human parturition regardless of whether the signals that trigger labour are of maternal and/or fetal origin. We found proteins from 33 genes with significantly altered expression profiles in relation to mode of labour and delivery. Most changes in labour occurred in proteins associated with 'immune and defence responses'. Although the signal transduction and regulation of these pathways varied among modes of delivery, hepatocyte nuclear factor 1 homeobox A emerged as a shared protein in the mechanism of labour. Moreover, several apolipoproteins such as apolipoprotein A-IV and APOE were found to change with labour, and these changes were also confirmed in maternal plasma. This study has identified significant protein changes in placental intervillous plasma with labour and has revealed several pathways related to human parturition.

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“…intracellular cyclic AMP levels [16]. As NOP is expressed in a high proportion of substance P (SP)/CGRP-positive neurons; and as a major subpopulation of N/OFQ neurons is located in juxtaposition to SP/CGRP-positive neurons; it is proposed that N/OFQ released locally in the dorsal root ganglia may (in a paracrine manner) modulate SP/ CGRP-containing neurons expressing NOP.…”

Section: Amentioning

confidence: 99%

Uterus-Relaxing Effects of Nociceptin and Nocistatin: Studies on Preterm and Term-Pregnant Human Myometrium In vitro

BH¹

2013

Reprod Sys Sexual Disorders

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The endogenous neuropeptides nociceptin/orphanin FQ and nocistatin translated from the prepronociceptin gene exert a relaxant effect on the rat uterus. Previous studies have reported their role in pain transmission in the central nervous system both in rodents and in humans, but to date only limited information is available on their effects in the periphery, and there are no data on their presence in the human uterus.The expression of prepronociceptin mRNA in the human uterus was confirmed by an RT-PCR technique. In vitro contractility studies of the action of nociceptin and nocistatin on human uterine tissues were performed in an isolated organ system. Human myometrial strips from cesarean sections at full-term pregnancy and at preterm labor were stimulated with oxytocin, and the relaxant effects of nociceptin and nocistatin were studied.The level of prepronociceptin mRNA was significantly decreased in full-term pregnant uterus samples as compared with preterm pregnancy samples. Nociceptin and nocistatin significantly and dose-dependently inhibited the oxytocinevoked contractions in the human uterus. In the presence of nocistatin, the uterus-relaxant effect of nociceptin was enhanced. In contrast, nociceptin did not alter the uterus-relaxant effect of nocistatin.We conclude that locally generated nociceptin and nocistatin both exert a relaxant effect on the human uterus, and nocistatin can potentiate the relaxant effect of nociceptin, though for this to occur nocistatin administration must precede the administration of nociceptin.

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Uterine Quiescence: The Role of Cyclic AMP

Cited by 47 publications

References 39 publications

TREK-1 currents in smooth muscle cells from pregnant human myometrium

TREK-1 currents in smooth muscle cells from pregnant human myometrium

Low abundance plasma proteins in labour

Uterus-Relaxing Effects of Nociceptin and Nocistatin: Studies on Preterm and Term-Pregnant Human Myometrium In vitro

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