Magnesium sulfate inhibits the oxytocin-induced production of inositol 1,4,5-trisphosphate in cultured human myometrial cells

William W. Hurd, Viswanathan Natarajan, John R. Fischer, Dawn M. Singh, Shawn G. Gibbs, Victor P. Fomin

Research output: Contribution to journalArticle

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Abstract

OBJECTIVE: The purpose of this study was to determine the effects of magnesium sulfate on inositol trisphosphate production and the mechanism of these effects. STUDY DESIGN: Myometrium was obtained at the time of cesarean delivery from women before labor at term. Inositol trisphosphate was measured in the primary myometrial cell cultures after stimulation with oxytocin, sodium fluoride, or Bay K 8644 with or without preincubation with magnesium sulfate or nifedipine. Experiments were performed in either calcium-containing or calcium-free medium that contained egtazic acid and after preincubation with the intracellular calcium chelator BAPTA-acetoxymethylester. Inositol trisphosphate production was measured by radioreceptor assay. In separate experiments, changes in intracellular calcium concentrations ([Ca2+]i) were measured with the use of Fura-2 and spectrophotofluorometry. RESULTS: Oxytocin, sodium fluoride, and Bay K 8644 increased inositol trisphosphate production 2- to 4fold. Preincubation with magnesium sulfate (3 × 10-3 mol/L) for ≥5 minutes decreased oxytocin-, sodium fluoride-, and Bay K 8644-induced inositol trisphosphate production in either calcium-containing or calcium-free media. Preincubation with BAPTA-acetoxymethylester decreased oxytocin-stimulated inositol trisphosphate production by 78% in calcium-containing media and completely prevented the oxytocin response in calcium-free media. Magnesium sulfate decreased inositol trisphosphate production in calcium-containing media but had no additional effect in calcium-free media. Oxytocin and Bay K 8644 increased [Ca2+]i in either calcium-containing or calcium-free media, and magnesium sulfate reduced this in both cases. CONCLUSION: Magnesium sulfate appears to inhibit phosphatidylinositol-4, 5-bisphosphate-specific phospholipase C activity and subsequent calcium release in cultured myometrial cells by a direct effect on phospholipase C.

Original languageEnglish (US)
Pages (from-to)419-424
Number of pages6
JournalAmerican Journal of Obstetrics and Gynecology
Volume187
Issue number2
DOIs
StatePublished - Aug 2002

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Magnesium Sulfate
Inositol 1,4,5-Trisphosphate
Oxytocin
Calcium
Inositol
3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester
Sodium Fluoride
Type C Phospholipases
Radioligand Assay
Primary Cell Culture
Myometrium
Fura-2
Egtazic Acid
Nifedipine
Phosphatidylinositols
Cultured Cells

Keywords

  • Calcium
  • Fura-2
  • Magnesium sulfate
  • Myometrium
  • Phospholipase C
  • Pregnancy

ASJC Scopus subject areas

  • Obstetrics and Gynecology

Cite this

Magnesium sulfate inhibits the oxytocin-induced production of inositol 1,4,5-trisphosphate in cultured human myometrial cells. / Hurd, William W.; Natarajan, Viswanathan; Fischer, John R.; Singh, Dawn M.; Gibbs, Shawn G.; Fomin, Victor P.

In: American Journal of Obstetrics and Gynecology, Vol. 187, No. 2, 08.2002, p. 419-424.

Research output: Contribution to journalArticle

Hurd, William W. ; Natarajan, Viswanathan ; Fischer, John R. ; Singh, Dawn M. ; Gibbs, Shawn G. ; Fomin, Victor P. / Magnesium sulfate inhibits the oxytocin-induced production of inositol 1,4,5-trisphosphate in cultured human myometrial cells. In: American Journal of Obstetrics and Gynecology. 2002 ; Vol. 187, No. 2. pp. 419-424.
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abstract = "OBJECTIVE: The purpose of this study was to determine the effects of magnesium sulfate on inositol trisphosphate production and the mechanism of these effects. STUDY DESIGN: Myometrium was obtained at the time of cesarean delivery from women before labor at term. Inositol trisphosphate was measured in the primary myometrial cell cultures after stimulation with oxytocin, sodium fluoride, or Bay K 8644 with or without preincubation with magnesium sulfate or nifedipine. Experiments were performed in either calcium-containing or calcium-free medium that contained egtazic acid and after preincubation with the intracellular calcium chelator BAPTA-acetoxymethylester. Inositol trisphosphate production was measured by radioreceptor assay. In separate experiments, changes in intracellular calcium concentrations ([Ca2+]i) were measured with the use of Fura-2 and spectrophotofluorometry. RESULTS: Oxytocin, sodium fluoride, and Bay K 8644 increased inositol trisphosphate production 2- to 4fold. Preincubation with magnesium sulfate (3 × 10-3 mol/L) for ≥5 minutes decreased oxytocin-, sodium fluoride-, and Bay K 8644-induced inositol trisphosphate production in either calcium-containing or calcium-free media. Preincubation with BAPTA-acetoxymethylester decreased oxytocin-stimulated inositol trisphosphate production by 78{\%} in calcium-containing media and completely prevented the oxytocin response in calcium-free media. Magnesium sulfate decreased inositol trisphosphate production in calcium-containing media but had no additional effect in calcium-free media. Oxytocin and Bay K 8644 increased [Ca2+]i in either calcium-containing or calcium-free media, and magnesium sulfate reduced this in both cases. CONCLUSION: Magnesium sulfate appears to inhibit phosphatidylinositol-4, 5-bisphosphate-specific phospholipase C activity and subsequent calcium release in cultured myometrial cells by a direct effect on phospholipase C.",
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AU - Natarajan, Viswanathan

AU - Fischer, John R.

AU - Singh, Dawn M.

AU - Gibbs, Shawn G.

AU - Fomin, Victor P.

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AB - OBJECTIVE: The purpose of this study was to determine the effects of magnesium sulfate on inositol trisphosphate production and the mechanism of these effects. STUDY DESIGN: Myometrium was obtained at the time of cesarean delivery from women before labor at term. Inositol trisphosphate was measured in the primary myometrial cell cultures after stimulation with oxytocin, sodium fluoride, or Bay K 8644 with or without preincubation with magnesium sulfate or nifedipine. Experiments were performed in either calcium-containing or calcium-free medium that contained egtazic acid and after preincubation with the intracellular calcium chelator BAPTA-acetoxymethylester. Inositol trisphosphate production was measured by radioreceptor assay. In separate experiments, changes in intracellular calcium concentrations ([Ca2+]i) were measured with the use of Fura-2 and spectrophotofluorometry. RESULTS: Oxytocin, sodium fluoride, and Bay K 8644 increased inositol trisphosphate production 2- to 4fold. Preincubation with magnesium sulfate (3 × 10-3 mol/L) for ≥5 minutes decreased oxytocin-, sodium fluoride-, and Bay K 8644-induced inositol trisphosphate production in either calcium-containing or calcium-free media. Preincubation with BAPTA-acetoxymethylester decreased oxytocin-stimulated inositol trisphosphate production by 78% in calcium-containing media and completely prevented the oxytocin response in calcium-free media. Magnesium sulfate decreased inositol trisphosphate production in calcium-containing media but had no additional effect in calcium-free media. Oxytocin and Bay K 8644 increased [Ca2+]i in either calcium-containing or calcium-free media, and magnesium sulfate reduced this in both cases. CONCLUSION: Magnesium sulfate appears to inhibit phosphatidylinositol-4, 5-bisphosphate-specific phospholipase C activity and subsequent calcium release in cultured myometrial cells by a direct effect on phospholipase C.

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KW - Fura-2

KW - Magnesium sulfate

KW - Myometrium

KW - Phospholipase C

KW - Pregnancy

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