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Journal of the Society for Gynecologic Investigation
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Effect of Cocaine on Intracellular Calcium Regulation in Myometrium From Pregnant Women

V. P. Fomin, PhD

Department of Obstetrics and Gynecology and Medicine, Indiana University Medical Center, Indianapolis, Indiana; vfomina{at}iupui.edu

D. M. Singh, BSc

H. L. Brown, MD

V. Natarajan, PhD

W. W. Hurd, MD

Department of Obstetrics and Gynecology and Medicine, Indiana University Medical Center, Indianapolis, Indiana

Objective: To evaluate the effect of cocaine on intracellular free calcium ([Ca2+]i) regulation in human myometrial cells by determining the sources of Ca2+ it might mobilize, as well as assess the role cocaine might play in the catecholamine's effect on the cell's [Ca2+]i.

Methods: Primary culture of myometrial cells from pregnant women was used as an experimental model. [Ca2+]i relative changes in response to cocaine and norepinephrine were measured with fura-2 fluorometry and analyzed bymeans of one-way analysisof variance.

Results: Cocaine alone (10-8 to 10-3 mol/L) increased [Ca2+]i by up to 43 ± 18% over basal level in a dose-dependent manner. Norepinephrine also elevated [Ca2+]i in a concentration-dependent manner (202 ± 24% over basal level at 10-4 mol/L). The norepinephrine-evoked increase was inhibited in Ca2+-free media by 48% whereas the cocaine response was not affected. The Ca2+-channel antagonist nifedipine caused decrease in the [Ca2+]i response to 10-5 mol/L of norepinephrine by 48%, whereas the [Ca2+]i rise to 10-5 mol/L cocaine was not significantly chaned. Inhibitor of the sarcoplasmic reticulum Ca2+ pump, thapsigargin, completely blocked cocaine-evoked increases in [Ca2+]i, whereas norepinephrine response were greatly reduced. At the same time, cocaine (10-8 to 10-3 mol/L) did not potentiate norepinephrine-evoked Ca2+]i, increases in the cells.

Conclusion: These results indicate that cocaine increases [Ca2+]i in pregnant human myometrial cells, primarily by stimulating release of Ca2+ from intracefullar stores rather than by direct stimulation of Ca2+ influx.

Key Words: Cocaine • myometrium • intracellular calcium • human • cell culture

Journal of the Society for Gynecologic Investigation, Vol. 6, No. 3, 147-152 (1999)
DOI: 10.1177/107155769900600306
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