Effect of Cocaine on Intracellular Calcium Regulation in Myometrium From Pregnant Women

Abstract

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.