A role for phosphoinositide hydrolysis in human uterine smooth muscle during parturition

Schrey, M.P.; Cornford, Philip; Read, Alison M.; Steer, Philip

doi:10.1016/s0002-9378(88)80182-0

Cited by 92 publications

(24 citation statements)

References 15 publications

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“…We found that oxytocin strongly and PGs (PGE2 and PGF2~) slightly stimulated phosphoinositide hydrolysis and IP production. Similar findings for the response to oxytocin have been reported in the guinea pig (Marc et al 1988), rat (Anwer and Sanborn 1989) and human myometrium (Schrey et al 1988), as well as in the sheep (Flint et al 1986) and human endometrium (Schrey et al 1986). Conflicting views are held about the effects of PGE2 and PGF2~ on IP production in myometrium.…”

Section: Discussionsupporting

confidence: 79%

“…In myometrium, various kinds of receptor agonists including neurotransmitter such as norepinephrine (Ruzycky and Triggle 1987;Schrey et al 1988), and mediators of uterine contractility such as oxytocin (Marc et al 1986), PGs (Ruzycky and Triggle 1987), platelet-activating factor (Voral et al 1989), endothelin-1 (Okawa et al 1990) were studied for their effect on phosphoinositide breakdown.…”

Section: Introductionmentioning

confidence: 99%

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Oxytocin, PGE2 and PGF2α stimulate the production of inositol phosphates in the rabbit myometrium

Okawa

Suzuki

Endo

et al. 1993

Arch Gynecol Obstet

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Phosphoinositide breakdown is thought to be important in regulating a variety of transmembrane signal transduction in the action of oxytocic agent during uterine smooth muscle contraction. We investigated the effects of oxytocin and prostaglandins (PGE2 and PGF2 alpha) on phosphoinositide hydrolysis in the myometrium taken from non-pregnant and pregnant rabbits by measuring the accumulation of total inositol phosphates (IP). Oxytocin strongly, and PGE2 and PGF2 alpha slightly but significantly, stimulated IP production in both the non-pregnant and pregnant myometria. Oxytocin more markedly accelerated the IP production in pregnant myometrium than in non-pregnant myometrium. However, IP production stimulated by PGE2 and PGF2 alpha was much the same in non-pregnant and pregnant myometria. The amount and time course of the increase in the production of the total IPs by oxytocin are quite different from those by PGs. It seems that the mechanism by which oxytocin stimulates phospholipase C is different from that of the PGs. It is suggested that transmembrane signalling pathways of phosphoinositide hydrolysis play an important role in the each mechanism.

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Section: Discussionsupporting

confidence: 79%

Section: Introductionmentioning

confidence: 99%

Oxytocin, PGE2 and PGF2α stimulate the production of inositol phosphates in the rabbit myometrium

Okawa

Suzuki

Endo

et al. 1993

Arch Gynecol Obstet

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“…Agonists such as oxytocin, PG F 2 a, endothelin-1, and acetylcholine increase intracellular Ca 2C concentrations ([Ca 2C ]i) and induce myometrial contractions (Anwer & Sanborn 1989, Sakata et al 1989, Sakata & Karaki 1992, Wray 1993, Szal et al 1994, Kim et al 1995. After the agonists bind to their respective receptors, phosphoinositide (PI) turnover occurs in uterine smooth muscle cells (Marc et al 1986, Schrey et al 1988, Schiemann et al 1991 and two important signal transduction molecules, inositol 1,4,5-trisphosphate and diacylglycerol, are produced. Inositol 1,4,5-trisphosphate releases Ca 2C from intracellular Ca 2C stores and activates calmodulin.…”

Section: Introductionmentioning

confidence: 99%

Role of protein kinase Cβ in rhythmic contractions of human pregnant myometrium

Yasuda

Nakamoto²,

Yasuhara³

et al. 2007

Reproduction

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To assess the role of protein kinase Cb (PKCb) in human myometrial contractions during pregnancy, we evaluated the effect of a PKCb inhibitor (LY333531) on the pregnant and nonpregnant myometrial contractions and compared the level of PKCb in the pregnant myometrium with that in the nonpregnant myometrium. The effects of LY333531 on the myometrial contractions were examined by measuring contractile activity (frequency and amplitude). PKCb in human myometrium was assessed at mRNA level using real-time PCR method. The characteristics of contractile activity were different between the pregnant and the nonpregnant myometrium. The amplitude of rhythmic contractions in the preterm and term myometrium was increased 2-to 2.5-fold when compared with that in the nonpregnant myometrium, but the frequency of rhythmic contractions was decreased by about half. LY333531 (10 K6 M) reduced the increased amplitude in the preterm and term myometrium by about 50%, and the inhibitory effects of LY333531 in the pregnant myometrium were significantly greater than that in the nonpregnant myometrium (about 50 vs 25%). However, the frequency in the pregnant and nonpregnant myometrium was not influenced by LY333531. Real-time PCR revealed a significant, five-to sevenfold increase in the expression of PKCb mRNA in the preterm and term myometrium when compared with the nonpregnant myometrium. These findings suggest that the increased amplitude of human myometrial contractions during pregnancy is related to the increased level of PKCb. A PKCb inhibitor may reduce preterm uterine contractions and prevent preterm delivery.

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“…These receptor agonists stimulate phosphoinositide turnover in the uterine smooth muscle (4,5). In various types of smooth muscle, inositol 1,4,5,-trisphosphate, one of the phosphoinositide hydrolysis products, releases Ca 2+ from the intracellular Ca2+ store and induces transient contraction (6).…”

mentioning

confidence: 99%

Increased Inhibitory Effect of Phorbol Ester on Cytosolic Ca2+ Level and Contraction in Rat Myometrium after Gestation

Ozaki

Hori

Karaki

1996

Japanese Journal of Pharmacology

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ABSTRACT-Activation of voltage-dependent Ca 21 channels by high K+ (40 mM) increased the cytosolic Ca2+ level ([Ca 2+]i) (estimated by fura-PE3 fluorescence ratio) and force in myometrium isolated from pregnant (21 days after gestation) and non-pregnant (estrus) rats. 12-Deoxyphorbol 13-isobutyrate (DPB, 1 mM) decreased the high K+-stimulated [Ca 2+]i and force in a concentration-dependent manner. The inhibitory effect was stronger in the pregnant myometrium than in the non-pregnant myometrium. In the pregnant myometrium, the increase in Ca 21 permeability by ionomycin (1 uM) greatly increased [Ca 2+]i and force, which were only partially inhibited by verapamil (10 pM). DPB (1 pM) inhibited the verapamilinsensitive component of the increases in [Ca 2+]i and muscle tension. Oxytocin (100 nM) and thapsigargin (1 pM) also induced a verapamil-insensitive increase in [Ca 2+]i and force, and DPB (1 pM) inhibited these increments. Ca2+ sensitivity of contractile elements, estimated from the relationships between Ca 2+ and muscle force in intact and a-toxin permeabilized muscle, was not significantly changed by DPB (1 pM). In summary, DPB inhibits the increase in [Ca 21]i more strongly in myometrium isolated from pregnant rats than that from non-pregnant rats without any change in the [Ca 2+]i/tension relationship. Since DPB decreased [Ca 2+]i-rise induced by three different mechanisms, DPB may activate Ca 2+ extrusion, rather than to inhibit a specific influx pathway, to decrease [Ca 2+]i.Keywords: Uterine smooth muscle, Phorbol ester, Relaxation, Cytosolic Ca2+ level, Pregnancy It is well-known that uterotonic agonists, such as oxytocin, carbachol and prostaglandins, increase intracellular Ca2+ concentration ([Ca 2+]i) and contraction (1-3). These receptor agonists stimulate phosphoinositide turnover in the uterine smooth muscle (4, 5). In various types of smooth muscle, inositol 1,4,5,-trisphosphate, one of the phosphoinositide hydrolysis products, releases Ca 2+ from the intracellular Ca2+ store and induces transient contraction (6). Another phosphoinositide product, diacylglycerol, stimulates protein kinase C that phosphorylates various proteins involved in cellular function (7). It has been reported that protein kinase C activation with phorbol ester inhibits smooth muscle contraction by inhibiting Ca 2+ channel activity or inositol phosphate production (8, 9), while it induces contraction by activation of contractile proteins (10-12). In cultured cells from rat portal vein, phorbol esters increase Ca 2-7 channel activity (13). In myometrium, it has been reported that phorbol ester induces stimulatory and inhibitory effects on contraction (14-16). However, few attempts have been made to compare the role of protein kinase C before and after pregnancy. In the present studies, we compared the effect of protein kinase C activation by phorbol esters on [Ca 2+]i and muscle contraction in isolated uterine smooth muscle from non-pregnant and pregnant rats. Female Wistar rats (200-250 g; Shiraishi Laboratory Animals, Tokyo...

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A role for phosphoinositide hydrolysis in human uterine smooth muscle during parturition

Cited by 92 publications

References 15 publications

Oxytocin, PGE2 and PGF2α stimulate the production of inositol phosphates in the rabbit myometrium

Oxytocin, PGE2 and PGF2α stimulate the production of inositol phosphates in the rabbit myometrium

Role of protein kinase Cβ in rhythmic contractions of human pregnant myometrium

Increased Inhibitory Effect of Phorbol Ester on Cytosolic Ca2+ Level and Contraction in Rat Myometrium after Gestation

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