Magnesium sulfate inhibits the oxytocin-induced production of inositol 1,4,5-trisphosphate in cultured human myometrial cells.
OBJECTIVE
The purpose of this study was to determine the effects of magnesium sulfate on inositol trisphosphate production and the mechanism of these effects.


METHODS
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 ([Ca(2+)](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 4-fold. Preincubation with magnesium sulfate (3 x 10(-3) mol/L) for > or = 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 [Ca(2+)](i) in either calcium-containing or calcium-free media, and magnesium sulfate reduced this in both cases.


CONCLUSIONS
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.
Hurd
William W
WW
Department of Obstetrics and Gynecology, Wright State University School of Medicine, Dayton, Ohio, USA. william.hurd@wright.edu
Natarajan
Viswanathan
V
Fischer
John R
JR
Singh
Dawn M
DM
Gibbs
Shawn G
SG
Fomin
Victor P
VP
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000037:antagonists & inhibitors / Q000378:metabolism; D002118:Calcium / Q000037:antagonists & inhibitors / Q000378:metabolism; D002120:Calcium Channel Agonists / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D004347:Drug Interactions; D004533:Egtazic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D005260:Female; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000096:biosynthesis*; D008278:Magnesium Sulfate / Q000494:pharmacology*; D009215:Myometrium / Q000187:drug effects / Q000378:metabolism*; D009543:Nifedipine / Q000494:pharmacology; D010121:Oxytocin / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D012969:Sodium Fluoride / Q000037:antagonists & inhibitors / Q000378:metabolism
D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; D010121:Oxytocin; D004533:Egtazic Acid; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D008278:Magnesium Sulfate; D015544:Inositol 1,4,5-Trisphosphate; D012969:Sodium Fluoride; D009543:Nifedipine; D002118:Calcium