Magnesium sulfate inhibits oxytocin-induced calcium mobilization in human puerperal myometrial cells: Possible involvement of intracellular free magnesium concentration

Mizuki, Jirou; Tasaka, Keiichi; Masumoto, Nobuyuki; Kasahara, Kanji; Miyake, Akira; Takahashi, Osamu

doi:10.1016/0002-9378(93)90147-b

Cited by 41 publications

(15 citation statements)

References 22 publications

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“…Inhibition of relaxation would enhance the direct, oxytocin-induced increases in myometrial contractility that result from activation of phospholipase C-␤ [2,3] or from effects on Ca 2ϩ channels [7,28,29]. Desensitization of the pathway that stimulates adenylyl cyclase by chronic oxytocin exposure is most likely to be important in vivo when oxytocin receptor concentrations are greatest, just before parturition.…”

Section: Discussionmentioning

confidence: 99%

Chronic Oxytocin Pretreatment Inhibits Adenylyl Cyclase Activity in Cultured Rat Myometrial Cells1

Lindeman

Hirshman

Kuhl

et al. 1998

Biology of Reproduction

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To determine whether chronic oxytocin pretreatment inhibits adenylyl cyclase, we compared adenylyl cyclase activity in membranes prepared from cultured, immortalized rat myometrial cells that were untreated or pretreated for 24 h with oxytocin. Chronic oxytocin pretreatment (1 x 10(-5) M for 24 h) attenuated basal, guanosine triphosphate (1 x 10(-5) M)-, isoproterenol (1 x 10(-4) M)-, forskolin (1 x 10(-5) M)-, MnCl2 (20 mM)- or NaF (1 x 10(-2) M)-stimulated adenylyl cyclase activity by 27 +/- 5% to 39 +/- 11% (n = 6, p < 0.05). Oxytocin pretreatment for 2 h (n = 5) did not produce a significant effect. To understand the mechanism by which oxytocin pretreatment decreased activity of the adenylyl cyclase pathway, we compared effects of pretreatment with either oxytocin or phenylephrine on adenylyl cyclase activity and determined the effects of Gi inhibition and protein kinase C (PKC) depletion. Chronic (24 h) phenylephrine pretreatment (1 x 10(-4) M) had effects similar to those of oxytocin pretreatment (1 x 10(-5) M). PKC depletion with phorbol 12-myristate 13-acetate (1 x 10(-6) M, 41 h) prevented attenuation of adenylyl cyclase activity by oxytocin pretreatment (1 x 10(-5) M for 24 h). Inhibition of Gi by pertussis toxin pretreatment (1.25 microg/ml, 41 h) had no significant effect. These findings suggest that chronic oxytocin pretreatment desensitizes the adenylyl cyclase pathway by a cross-regulatory mechanism that involves activation of Gq and PKC.

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Section: Discussionmentioning

confidence: 99%

Chronic Oxytocin Pretreatment Inhibits Adenylyl Cyclase Activity in Cultured Rat Myometrial Cells1

Lindeman

Hirshman

Kuhl

et al. 1998

Biology of Reproduction

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“…The basis for its use as a tocolytic is due to the observed effects of Mg in reducing myometrial contractility through extra-and intracellular mechanisms of action [30][31][32][33] . Its most widely recognized and well studied role in the brain is in relation to the NMDA glutamate receptor ion channel where it performs a physiological blocking action that prevents ion flow through the channel under conditions of normal membrane polarization.…”

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confidence: 99%

High Dose Magnesium Sulfate Exposure Induces Apoptotic Cell Death in the Developing Neonatal Mouse Brain

Dribben¹,

Creeley

Wang

et al. 2009

Neonatology

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Background: Magnesium sulfate (MgSO₄) is often used as a treatment for pre-eclampsia/eclampsia and preterm labor, resulting in the exposure of a significant number of neonates to this drug despite a lack of evidence suggesting that it is safe, or effective as a tocolytic. While there is evidence that MgSO₄ may be neuroprotective in perinatal brain injury, recent reviews have suggested that the effects are dependent upon dose, and that higher doses may actually increase neonatal morbidity and mortality. There is a lack of evidence investigating the neurotoxic effects of neonatal magnesium (Mg) exposure on the developing brain, specifically in terms of neurodevelopmental apoptosis, a cell-killing phenomenon known to be potentiated by other drugs with mechanisms of action at Mg-binding sites (i.e. NMDA receptor antagonists such as MK-801, ketamine, and PCP). Objective: To investigate the effects of Mg exposure on the neonatal mouse brain at different postnatal ages to determine whether MgSO₄ treatment causes significant cell death in the developing mouse brain. Methods: C57Bl/6 mice were treated with four doses of MgSO₄ (250 mg/kg) on postnatal days 3 (P3), 7 (P7) or 14 (P14). Caspase-3 immunohistochemistry, cupric silver staining, and electron microscopy techniques were used to examine Mg-treated brains for neurotoxic effects. Results: Qualitative evaluation using cupric silver staining revealed widespread damage throughout the brain in P7 animals. Results of electron microscopy confirmed that the cell death process was apoptotic in nature. Quantitative evaluation of damage to the cortex, caudate-putamen, hippocampus, thalamus, and cerebellum showed that Mg treatment caused significant brain damage in animals treated on P3 and P7, but not P14. Conclusions: Administration of high doses of Mg may be detrimental to the fetal brain, particularly if exposure occurs during critical periods of neurodevelopment.

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“…When 827 were surveyed about their practice patterns, 45% reported using magnesium sulfate as their first-line for preterm labor, and 41% used it as first-line for recurrent preterm labor (41%) [17]. Magnesium sulfate acts by inhibiting voltage-independent calcium channels at the myometrial cell surface, and likely has an intracellular mechanism of action as well [10,18,19]. Extracellular magnesium suppresses calcium influx across the cell membrane, whereas intracellular magnesium competes with calcium, thereby inhibiting myosin light-chain kinase activity.…”

Section: Magnesium Sulfatementioning

confidence: 98%

Prematurity prevention: the role of acute tocolysis

Blumenfeld

Lyell

2009

Current Opinion in Obstetrics &Amp; Gynecology

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All tocolytic medications have side-effects, some of them potentially life-threatening. Decisions regarding whether to use a tocolytic and which tocolytic to use require the diagnosis of preterm labor, knowledge of the patient's gestational age, medical conditions, and cost. Once tocolysis is initiated, attention must be paid to the patient's response, side-effects, and adverse events. Larger studies are needed which incorporate, in addition to efficacy, data on safety and side-effect profiles and cost.

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Magnesium sulfate inhibits oxytocin-induced calcium mobilization in human puerperal myometrial cells: Possible involvement of intracellular free magnesium concentration

Cited by 41 publications

References 22 publications

Chronic Oxytocin Pretreatment Inhibits Adenylyl Cyclase Activity in Cultured Rat Myometrial Cells1

Chronic Oxytocin Pretreatment Inhibits Adenylyl Cyclase Activity in Cultured Rat Myometrial Cells1

High Dose Magnesium Sulfate Exposure Induces Apoptotic Cell Death in the Developing Neonatal Mouse Brain

Prematurity prevention: the role of acute tocolysis

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