Victor P. Fomin

Effect of cocaine on intracellular calcium regulation in myometrium from pregnant women

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 catecholamines effect on the cells [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.

Cocaine augments contractility of the pregnant human uterus by both adrenergic and nonadrenergic mechanisms

OBJECTIVE Our purpose was to evaluate the mechanisms of cocaines effect on both spontaneous and agonist-induced contractility of pregnant human myometrium. STUDY DESIGN Myometrium was obtained from 42 women at term who were undergoing cesarean section. Myometrial strips were suspended in contraction baths and isometric contractions were measured. Tissue was exposed to various combinations of cocaine, prazosin, desipramine, benzoylecgonine, and procaine. Spontaneous contractility and the contractile responses to increasing concentrations of methoxamine and oxytocin were measured and compared. RESULTS Cocaine increased spontaneous myometrial contractility by more than threefold. Prazosin, an alpha-adrenergic antagonist, blocked this effect only for the first 35 minutes of exposure. The cumulative concentration-response to the alpha-adrenergic agonist methoxamine was increased by cocaine in terms of both sensitivity and maximal response. The maximal response to oxytocin, but not the sensitivity, was increased by cocaine by an effect that could not be blocked by prazosin. CONCLUSION Cocaine augments spontaneous and agonist-induced contractility of pregnant human myometrium by mechanisms that appear to be both alpha-adrenergic and nonadrenergic in nature.