Cellular mechanisms underlying magnesium sulfate inhibition of phasic myometrial contractions.
These studies sought to test the hypothesis that magnesium inhibits extracellular calcium entry, thereby inhibiting intracellular calcium release and cytosolic calcium oscillations in myometrial smooth muscle. In vitro contraction studies were performed using oxytocin and other uterotonic agonists with and without the addition of magnesium in the presence and absence of extracellular calcium. Cytosolic calcium studies were performed using myometrial strips loaded with Fura 2. Oxytocin produced cytosolic calcium oscillations and simultaneous phasic contractions; both were inhibited by magnesium. The other uterotonic agonists tested also produced phasic contractions which were significantly inhibited by magnesium. The magnesium effect was reversible with washout and counteracted by Bay K 8644 (a calcium channel agonist). In the absence of extracellular calcium, intracellular calcium release in response to oxytocin was inhibited by magnesium. In summary, magnesium inhibited extracellular calcium entry, intracellular calcium release, cytosolic calcium oscillations, and phasic contractions of myometrial smooth muscle.
Phillippe
M
M
Department of Obstetrics & Gynecology, University of Chicago, Chicago, Illinois, 60637, USA. mphillip@babies.bsd.uchicago.edu
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002120:Calcium Channel Agonists / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects; D005260:Female; D066298:In Vitro Techniques; D017136:Ion Transport / Q000187:drug effects; D008278:Magnesium Sulfate / Q000494:pharmacology*; D008954:Models, Biological; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D009215:Myometrium / Q000187:drug effects / Q000502:physiology; D010121:Oxytocin / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014590:Uterine Contraction / Q000187:drug effects* / Q000502:physiology*
D002120:Calcium Channel Agonists; D010121:Oxytocin; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D008278:Magnesium Sulfate; D002118:Calcium