Prostaglandins, Thromboxanes and the Pregnant Rat Uterus at Term

Phillips, Christine A.; Poyser, N.L.

doi:10.1111/j.1476-5381.1981.tb16773.x

Cited by 22 publications

(8 citation statements)

References 16 publications

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“…Using RIA, gas chromatography, and mass spectroscopy to measure PG release by term pregnant rat uterine tissue, it was determined that PGD 2 release Ͼ PGI 2 and Tx Ͼ PGE 2 and PGF 2␣ [27]. Chan selectively measured PGE 2 and PGF 2␣ in both uterine and placental tissues in the pregnant rat [2].…”

Section: Discussionmentioning

confidence: 99%

Changes in Expression of Contractile FP and Relaxatory EP2 Receptors in Pregnant Rat Myometrium during Late Gestation, at Labor, and Postpartum1

Brodt-Eppley

Myatt

1998

Biology of Reproduction

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Prostaglandins synthesized at parturition may act via specific myometrial receptors as mediators of uterine contractions. Several isoforms of eicosanoid (prostaglandin) receptors, identified by pharmacological means, are linked to contractile (FP, EP1, EP3) or relaxatory (EP2, EP4, IP, DP) intracellular pathways. Changes in mRNA expression of the contractile FP and the relaxatory EP2 receptor were measured in myometrium throughout gestation, at parturition, and postpartum. Timed pregnant rats were killed at 0900 h on Day 16, 18, 20, 21, 21.5, or 22 (parturition) of pregnancy or one day postpartum (n = 5 animals/group). A longitudinal section of myometrium was removed, total RNA was extracted, and semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) was performed for glyceraldehyde phosphate dehydrogenase (GAPDH), calponin, EP2, and FP receptor mRNA expression. Complementary DNA products were run on agarose gels and visualized, and the quantity of cDNA product was measured against a DNA mass ladder. RT-PCR product identity was confirmed by restriction enzyme cleavage. EP2 receptor mRNA expression was highest at Day 16 and declined significantly to Day 21.5 and one day postpartum (p < 0.05, Student-Newman-Keuls procedure). Expression of FP receptor mRNA was low at Day 16 of gestation and increased significantly until delivery (p < 0.05, ANOVA) at Day 22, then fell to prepartum levels at one day postpartum. Myometrial activity at parturition may change from an active quiescent to an active contractile state in concert with a decline in expression of the relaxatory EP2 receptors and up-regulation of contractile FP receptors.

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Section: Discussionmentioning

confidence: 99%

Changes in Expression of Contractile FP and Relaxatory EP2 Receptors in Pregnant Rat Myometrium during Late Gestation, at Labor, and Postpartum1

Brodt-Eppley

Myatt

1998

Biology of Reproduction

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“…PGF 2α contracts the guinea‐pig uterus and potentiates the contractile effect of ATP on guinea‐pig myometrium ( Dozi‐Vassilides et al ., 1976 ; Whalley & White, 1980a , 1980b ; Weichman & Tucker, 1982 ; Coleman & Parkington, 1988 ). PGl 2 contracts the rat uterus and potentiates the action of other spasmogens on this tissue ( Vane & Williams, 1973 ; Williams et al ., 1979 ; Phillips & Poyser, 1981 ). Consequently, the present findings are consistent with the hypothesis that the contractile actions of ATP, ATP, 2‐methylthio ATP, adenosine and UTP on the guinea‐pig uterus are mediated by prostaglandins, particularly PGF 2α and possibly also PGl 2 .…”

Section: Discussionmentioning

confidence: 99%

The effects of P2Y receptor agonists and adenosine on prostaglandin production by the guinea‐pig uterus

Aitken

Poyser

Hollingsworth

2001

British J Pharmacology

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1 This study has investigated the eects adenosine 5'-triphosphate (ATP), analogues of ATP, uridine 5'-triphosphate (UTP) and adenosine on prostaglandin output from the guinea-pig uterus superfused in vitro, and from guinea-pig endometrium and myometrium cultured for 24 h. 2 ATP, 2-methylthio ATP and adenosine increased the outputs of prostaglandin F 2a (PGF 2a ) and 6-keto-PGF 1a (re¯ecting PGI 2 production), and UTP increased the output of PGF 2a from the superfused guinea-pig uterus. These ®ndings support the hypothesis that the contractile eects of ATP, 2-methylthio ATP, UTP and adenosine are mediated by prostaglandins. 3 Suramin (a P2 receptor antagonist) and 8-sulphophenyltheophylline (an A receptor antagonist) blocked the stimulatory actions of ATP and adenosine, respectively, on PGF 2a output, suggesting that ATP acts on P2 receptors (probably of the P2Y type) and adenosine acts on A receptors in the guinea-pig uterus to increase PGF 2a production. 4 ATP, 2-methylthio ATP, a,b-methylene ATP, b,g-methylene ATP, UTP and adenosine increased the output of PGF 2a from guinea-pig endometrium and myometrium after 24 h of culture, with a greater stimulatory eect being exerted on the endometrium than on the myometrium. Little or no stimulatory eect was seen after 2 and 8 h of culture. In addition the eects of ATP, ATP analogues, UTP and adenosine on the outputs of PGE 2 and 6-keto-PGF 1a from cultured endometrium and myometrium were more variable, with both stimulation and inhibition being observed. 5 The stimulatory eects of ATP and adenosine on PGF 2a output from the endometrium and myometrium were associated with an increase in the prostaglandin synthesizing capacity of both tissues, due probably to an increase in the amount of prostaglandin H synthase present.

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“…myometrial contractions and establishing labor (10)(11)(12), understanding the regulation of PGE2 synthesis in amnion fibroblasts appears central in deciphering the mechanisms of human labor onset.…”

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confidence: 99%

Activation of prostaglandin EP4 receptor attenuates the induction of cyclooxygenase‐2 expression by EP2 receptor activation in human amnion fibroblasts: implications for parturition

Wang

Zhou

et al. 2019

FASEB j.

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Human amnion fibroblasts produce abundant prostaglandin E2 (PGE2), which plays a crucial role in parturition by stimulating not only myometrial contraction and cervical ripening but also the expression of the rate‐limiting enzyme in PGE2 synthesis—namely, cyclooxygenase‐2 (COX‐2). This feed‐forward induction of COX‐2 expression by PGE2 is mediated via its receptors coupled with the cAMP and PKA pathway and subsequent phosphorylation of the transcription factors cAMP‐response element binding protein (CREB) and signal transducer and activator of transcription 3 (STAT3). Although prostaglandin E receptor (EP)‐2 and EP4 for PGE2 are coupled with activation of the cAMP and PKA pathway, the exact roles of these 2 receptors in the regulation of COX‐2 expression in amnion fibroblasts remain to be determined. Here, we clarify this issue by employing human amnion tissue and fibroblasts with the long‐term objective of specific targeting of prostaglandin synthesis in prevention of preterm birth. We find that an EP2 agonist caused long‐lasting increases in CREB phosphorylation and COX‐2 expression, whereas an EP4 agonist induced only transient increases in CREB phosphorylation and COX‐2 expression in amnion fibroblasts. Moreover, only EP2 stimulation increased STAT3 phosphorylation, whereas only EP4 stimulation increased PI3K activity. EP4 antagonist or inhibition of PI3K enhanced the induction of CREB and STAT3 phosphorylation and COX‐2 expression by PGE2 or EP2 stimulation, which was attenuated by EP4 overexpression. Of interest, PGE2 and Cortisol, both well‐demonstrated stimulants of COX‐2 expression in amnion fibroblasts, increased EP2 but decreased EP4 receptor expression. Furthermore, increased EP2 but decreased EP4 abundance were observed in amnion tissue at parturition. We conclude that EP2 and EP4 receptors play different roles in the regulation of COX‐2 expression in human amnion fibroblasts. EP2 is the dominant PGE2 receptor mediating the induction of COX‐2 at parturition, which can be attenuated by simultaneous activation of PI3K coupled to the EP4 receptor.—Lu, J.‐W., Wang, W.‐S., Zhou, Q., Gan, X.‐W., Myatt, L., Sun, K. Activation of prostaglandin EP4 receptor attenuates the induction of cyclooxygenase‐2 expression by EP2 receptor activation in human amnion fibroblasts: implications for parturition. FASEB J. 33, 8148–8160 (2019). http://www.fasebj.org

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Prostaglandins, Thromboxanes and the Pregnant Rat Uterus at Term

Cited by 22 publications

References 16 publications

Changes in Expression of Contractile FP and Relaxatory EP2 Receptors in Pregnant Rat Myometrium during Late Gestation, at Labor, and Postpartum1

Changes in Expression of Contractile FP and Relaxatory EP2 Receptors in Pregnant Rat Myometrium during Late Gestation, at Labor, and Postpartum1

The effects of P2Y receptor agonists and adenosine on prostaglandin production by the guinea‐pig uterus

Activation of prostaglandin EP4 receptor attenuates the induction of cyclooxygenase‐2 expression by EP2 receptor activation in human amnion fibroblasts: implications for parturition

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