Multiple mechanisms involved in oxytocin-induced modulation of myometrial contractility

Shmygol, Anatoly; Gullam, Joanna; Blanks, Andrew M.; Thornton, Steven

doi:10.1111/j.1745-7254.2006.00393.x

Cited by 71 publications

(47 citation statements)

References 46 publications

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“…It is the strongest uterotonic agent known and is commonly used in obstetrical practice to augment labor (Shmygol et al, 2006). In addition, the synthetic long-acting oxytocin analog carbetocin is widely used to prevent or treat postpartum hemorrhage (Peters and Duvekot, 2009).…”

Section: Discussionmentioning

confidence: 99%

“…It stimulates uterine contraction in a concentration-dependent manner by increasing intracellular calcium primarily through production of InsP 3 and release from the sarcoplasmic reticulum (Wray, 2007). It has, however, been noted that prolonged treatment with thapsigargin to deplete the sarcoplasmic reticulum does not eliminate oxytocin-induced contractions (Shmygol et al, 2006), suggesting other processes may be involved. The non-InsP 3 component has been most commonly explained by the action of RhoA, which activates Rho kinase to sensitize the contractile machinery to calcium (Kimura et al, 1996).…”

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confidence: 93%

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A Functional Role for Nicotinic Acid Adenine Dinucleotide Phosphate in Oxytocin-Mediated Contraction of Uterine Smooth Muscle from Rat

Aley

Noh²,

Gào³

et al. 2010

J Pharmacol Exp Ther

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Conventionally, G protein-coupled receptors are thought to increase calcium via inositol 1,4,5-trisphosphate (InsP 3 ). More recent evidence shows that an alternative second messenger, nicotinic acid adenine dinucleotide phosphate (NAADP), also has a role to play, causing researchers to question established calcium releasing pathways. With the recent development, by our group, of cell-permeant NAADP (NAADP-aceteoxymethyl ester) and a selective NAADP receptor antagonist (Ned-19; 1-(3-((4-(2-fluorophenyl)piperazin-1-yl)methyl)-4-methoxyphenyl)-2,3,4,9-tetrahydro-1H-pyrido [3,4-b]indole-3-carboxylic acid), the ability to investigate this signaling pathway has improved. Therefore, we investigated a role for NAADP in oxytocin-mediated responses in the rat uterus. Oxytocin-and NAADP-mediated effects were investigated by using contractile measurements of whole uterine strips from rat in organ baths. Responses were correlated to calcium release in cultured rat uterine smooth muscle cells measured by fluorescence microscopy. Inhibition of both oxytocin-induced contraction and calcium release by the traditional NAADP-signaling disrupter bafilomycin and the NAADP receptor antagonist Ned-19 clearly demonstrated a role for NAADP in oxytocin-induced signaling. A cell-permeant form of NAADP was able to produce both uterine contractions and calcium release. This response was unaffected by depletion of sarcoplasmic reticulum stores with thapsigargin, but was abolished by both bafilomycin and Ned-19. Crucially, oxytocin stimulated an increase in NAADP in rat uterine tissue. The present study demonstrates directly that NAADP signaling plays a role in rat uterine contractions. Moreover, investigation of this signaling pathway highlights yet another component of oxytocin-mediated signaling, stressing the need to consider the action of new components as they are discovered, even in signaling pathways that are thought to be well established.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 93%

A Functional Role for Nicotinic Acid Adenine Dinucleotide Phosphate in Oxytocin-Mediated Contraction of Uterine Smooth Muscle from Rat

Aley

Noh²,

Gào³

et al. 2010

J Pharmacol Exp Ther

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“…In addition to regulating smooth muscle contractility by electromechanical coupling, membrane potential independent, pharmacomechanical coupling can also be accounted for the physiological mechanisms that regulate contractions [36]. Activation of OTR in human myometrium can convert inactive RhoA-GDP to its active form, RhoA-GTP through guanine nucleotide exchange factors (GEFs) [37]. RhoA-GTP acts via Rho kinase (ROCK) to phosphorylate the regulatory subunit of MLC, leading to contractions.…”

Section: Previously Established Roles Of Ot/otr Systemmentioning

confidence: 99%

Advances in the role of oxytocin receptors in human parturition

Kim

Bennett

Terzidou

2017

Molecular and Cellular Endocrinology

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“…The effects of the misoprostol were investigated [33] . Oxytocin and misoprostol, because of their uterotonic property, are used in gynecology and obstetrics to induce and/or facilitate labour [18,34,35] .…”

Section: Discussionmentioning

confidence: 99%

“…Thus, in this paper, data investigating the following aspects were presented: (1) the effects on spontaneous contractions, (2) the effects on Ca 2+ mobilization and depolarizing action and (3) a comparison with those of two pharmacodynamic substances (Oxytocin and misoprostol) known and commonly used in obstetrical practice to stimulate labour [18] .…”

Section: Introductionmentioning

confidence: 99%

Effects of Sesamum Radiatum Aqueous Leaf Extract on Rhythmic Contractions of Uterine Smooth Muscle Bundles From Pregnant Rats

Konan¹,

Bouafou²,

Kouakou³

et al. 2012

LSMR

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Abstract-Sesamum radiatum is employed in traditional medicine for parturient women to facilitate deliveries. In this study, the effects of the aqueous leaf extract were examined on the contractile activity of uterine smooth muscle isolated from pregnant Wistar rats (19-21 days). The isometric contractile force of the uterine smooth muscle bundles was recorded by using a strain gauge. S. radiatum aqueous leaf extracts (ESera, 1×10 -4 µg/ml -100µg/ml) showed uterotonic properties. These uterotonic effects were characterized by the increase of the amplitude, the frequency and the basal tone of the uterine smooth muscle strips in normal Mac Ewen solution and by the development of contracture in depolarizing solution and in solution without calcium. Similar effects were observed with Oxytocin (OT, 2.5×10 -14 µg/ml -2.5×10 -9 µg/ml) and misoprostol (Miso, 1×10 -3 µg/ml -0.08µg/ml). In Ca 2+-free solution, the addition of the ESera (10 µg / ml) elicited the development of contracture in the presence of EGTA (0.1 mM). This result suggests that ESera could act on the double calcium flux (intracellular and extracellular) like misoprostol, a synthetic analogue of prostaglandin E 1 . In conclusion, the aqueous leaf extract of S. radiatum (ESera) had uterotonic effects (prostaglandin-like activity) on uterine contraction in pregnant rats.

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Multiple mechanisms involved in oxytocin-induced modulation of myometrial contractility

Cited by 71 publications

References 46 publications

A Functional Role for Nicotinic Acid Adenine Dinucleotide Phosphate in Oxytocin-Mediated Contraction of Uterine Smooth Muscle from Rat

A Functional Role for Nicotinic Acid Adenine Dinucleotide Phosphate in Oxytocin-Mediated Contraction of Uterine Smooth Muscle from Rat

Advances in the role of oxytocin receptors in human parturition

Effects of Sesamum Radiatum Aqueous Leaf Extract on Rhythmic Contractions of Uterine Smooth Muscle Bundles From Pregnant Rats

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