Abstract
Objective
It has been well established that oxytocin (OXT) increases intracellular free calcium ([Ca2+]i) by targeting both intracellular and extracellular stores, but the mechanisms involved in the increase through activation with prostaglandin F2α (PGF2α) are still incompletely understood. This study was designed to elucidate the source(s) of increased [Ca2+]i in response to PGF2α (10−6 M) or OXT (10−8 M) administration in the near-term rat myometrium.
Methods
The animals were divided into an in vitro group (n = 8), where the developed tension of uterine strips was assessed, and an in vivo group (n = 5), where a lobe of the uterus with intact innervation and circulation was loaded with the fluorescent indicator Indo-1 AM to assess [CA2+]i.
Results
PGF2α and OXT induced a 30.1% and 35.9%, respectively, increase in developed tension in the potassium chloride-depolarized myometrial strips. Nifedipine reduced the PGF2α and OXT increased tension by 65.8% and 49.4%, respectively. In vivo, both PGF2α and OXT increased [Ca2+]i in the pottassium chloride-depolarized uterine muscle by 35.7% and 44.6%, respectively, increases similar to the rises in tension in vitro. Nifedipine reduced these effects of PGF2α and OXT by 45.3% and 39.6%.
Conclusions
These findings indicate that in near-term myometrium the source of increased [Ca2+]i after administration of PGF2α, similar to OXT, is both extracellular and intracellular.
Similar content being viewed by others
References
Sanborn BM. Relationship of ion channel activity to control of myometrial calcium. J Soc Gynecol Investig 2000;7:4–11.
Taggart MJ, Wray S. Occurrence of intracellular pH transients during spontaneous contractions in rat uterine smooth muscle. J Physiol (Lond) 1993;472:23–31.
Anwer K, Howington JA, Sanborn BM. Antagonism of contractants and relaxants at the level of intracellular calcium and phosphoinositide turnover in the rat uterus. Endocrinolgy 1989;124:2995–3002.
Tasaka K, Masumoto N, Miyake A, Tanizawa O. Direct measurement of intracellular free calcium in cultured human puerperal myometrial cells stimulated by oxytocin: Effects of extracellular calcium and calcium channel blockers. Obstet Gynecol 1991;77:101–6.
Csapo AI. Smooth muscle as a contractile unit. Physiol Rev 1962;42:7–33.
Kawarabayashi T, Kishikawa T, Sugimori H. Effect of oxytocin on spontaneous electrical and mechanical activities in pregnant human myometrium. Am J Obstet Gynecol 1986;155:671–6.
Szal AE, Repke JT, Seely EW, Graves SW, Parker CA, Morgan KG. [Ca2+]i signaling in pregnant human myometrium. Am J Physiol 1994;267:E77–E87.
Phillippe M, Chien EK. Potassium chloride effects on the hormonal signal transduction mechanisms underlying phasic myometrial contractions. J Endocrinol 1995;146:485–93.
Izumi H, Bian K, Bukoski RD, Garfield RE. Agonists increase the sensitivity of contractile elements for Ca2+ in pregnant rat myometrium. Am J Obstet Gynecol 1996;175:175–99.
Molnar M, Hertelendy F. Regulation of intracellular free calcium in human myometrial cells by prostaglandin F2α: Comparison with oxytocin. J Clin Endocrinol Metab 1990;71:1243–50.
Parkington HC, Tonta M, Brennecke SP, Coleman HA. Contractile activity, membrane potential and cytoplasmic calcium in human uterine smooth muscle in the third trimester of pregnancy and during labor. Am J Obstet Gynecol 1999;181:1445–51.
Parkington HC, Tonta MA, Davies NK, Brennecke SP, Coleman HA. Hyperpolarization and slowing of the rate of contraction in human uterus in pregnancy by prostaglandin E2 and F2α: Involvement of the Na+ pump. J Physiol (Lond) 1999;514:229–43.
Inoue Y, Shimamura K, Sperelakis N. Oxytocin actions on voltage-dependent ionic channels in pregnant rat uterine smooth muscle cells. Can J Physiol Pharmacol 1992;70:1597–603.
Schrey MP, Cornford PA, Read AM, Steer PJ. A role for phosphoinositide hydrolysis in human myometrial smooth muscle during parturition. Am J Obstet Gynecol 1988;159:967–70.
Phillippe M, Sounders T, Basa A. Intracellular mechanisms underlying prostaglandin F2α-stimulated phasic myometrial contractions. Am J Physiol 1997;273:E665–73.
Ruttner Z, Ligeti L, Ivanics T, Slaaf DW, Reneman RS, Toth A. A novel model for the in vivo monitoring of uterine microcirculation and intracellular free calcium changes is rat. Microvasc Res 2000;59:213–20.
Toth A, Ivanics T, Ruttner Z, Slaff DW, Reneman RS, Ligeti L. Quantitative assessment of [Ca2+]i levels in rat skeletal muscle in vivo. Am J Physiol 1998;275:H1652–62.
Ruttner Z, Ligeti L, Reinlib L, Hines K, McLaughlin AC. Monitoring of intracellular free calcium in perfused rat liver. Cell Calcium 1993;14:465–72.
Phaneuf S, Europe-Finner GN, Varney M, MacKenzie IZ, Watson SP, Lopez-Bernal A. Oxytocin stimulated phosphoinositide hydrolysis in human myometrial cells: Involvement of pertussis toxin-sensitive and insensitive G proteins. J Endocrinol 1993;136:497–509.
Deleers M, Grognet P, Brasseur R. Structural considerations for calcium ionophoresis by prostaglandins. Biochem Pharmacol 1985;34:3831–6.
Carr DB, Clark AL, Kernek K, Spinnato JA. Maintenance oral nifedipine for preterm labor: A randomized clinical trial. Am J Obstet Gynecol 1999;181:822–7.
Author information
Authors and Affiliations
Corresponding author
Additional information
This work was supported by grants from OTKA (T026477, Hungary) and NWO (N19588, N028769 The Netherlands).
Rights and permissions
About this article
Cite this article
Ruttner, Z., Ivanics, T., Slaaf, D.W. et al. In Vivo Monitoring of Intracellular Free Calcium Changes During Uterine Activation By Prostaglandin F2α and Oxytocin. Reprod. Sci. 9, 294–298 (2002). https://doi.org/10.1177/107155760200900507
Published:
Issue Date:
DOI: https://doi.org/10.1177/107155760200900507