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

Academic Article

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 elect 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 by means of one-way analysis of 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 84%, whereas the [Ca2+](i) rise to 10-5 mol/L cocaine was not significantly changed. Inhibitor of the sarcoplasmic reticulum Ca2+ pump, thapsigargin, completely blocked cocaine-evoked increases in [Ca2+](i), whereas norepinephrine responses 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 intracellular stores rather than by direct stimulation of Ca2+ influx.
  • Authors

    Digital Object Identifier (doi)

    Author List

  • Fomin VP; Singh DM; Brown HL; Natarajan V; Hurd WW
  • Start Page

  • 147
  • End Page

  • 152
  • Volume

  • 6
  • Issue

  • 3