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The Mechanisms Underlying Bay K 8644-Stimulated Phasic Myometrial Contractions

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Abstract

Objective

Phasic myometrial contractions appear to be produced by calcium transients resulting from the activation of the phosphatidylinositol-signaling pathway. Bay K 8644, an L-type calcium channel activator, produces an increase in frequency and intensity of phasic myometrial contractions. These studies were performed to test the hypothesis that Bay K 8644—stimulated contractions were mediated through mechanisms involving phosphoinositide-specific phospholipase C activation and cytosolic calcium oscillation-like mechanisms.

Methods

In vitro contraction studies and intracellular calcium imaging were performed on longitudinal strips of uterine tissue obtained from mature virgin Sprague-Dawley rats. Isometric contraction data were computer digitized, analyzed for contraction area, and normalized for cross-sectional area. Dose-response studies were performed using previously reported inhibitors of cytosolic calcium oscillation mechanisms. In addition, qualitative inositol-phosphate production studies were performed after prelabeling uterine tissue in vitro with 3H-inositol. Subsequently, the labeled inositol phosphates were separated and recovered using anion exchange chromatography.

Results

Bay K 8644 produced periodic calcium transients or oscillations along with a dose-related increase in contractile activity and a significant increase in inositol-phosphate production. In contrast, neomycin (an inhibitor of phospholipase C), adenine (an inhibitor of calcium-induced calcium release), nifedipine (an L-type calcium channel blocker), and EGTA (a calcium chelator) significantly inhibited Bay K 8644-stimulated contractile activity.

Conclusions

These results are consistent with the hypothesis that Bay K 8644, through its facilitation of increased intracellular calcium, results in the activation of the phosphatidylinsitol-signaling pathway and cytosolic calcium oscillation-like phenomena, thereby resulting in the generation of phasic myometrial contractions.

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, MC 2050, University of Chicago Hospitals, 5841 S. Maryland Avenue, Chicago, Illinois, 60637, USA

    Edward K. Chien MD, T. Saunders & M. Phillippe MD

Authors
  1. Edward K. Chien MD
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  2. T. Saunders
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  3. M. Phillippe MD
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Additional information

This research was funded by the National Institute of Child Health and Human Development (HD22063).

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Chien, E.K., Saunders, T. & Phillippe, M. The Mechanisms Underlying Bay K 8644-Stimulated Phasic Myometrial Contractions. Reprod. Sci. 3, 106–112 (1996). https://doi.org/10.1016/1071-5576(96)00006-8

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