Effect of cocaine on cytoplasmic calcium and IP3 production in human myometrial cells

Academic Article

Abstract

  • Cocaine has ability to increase spontaneous myometrial contractions as well as to potentiate the contractile responses to catecholamines. Because free cytoplasmic calcium concentration ([Ca2+]i) and inositol 1,4,5-trisphosphate (IP3) are important messengers of uterine contraction, we evaluated the effect of cocaine on [Ca2+]i and IP3 generation in primary culture of myometrial cells from pregnant women. [Ca2+]i and IP3 were measured using fura-2 and radioligand binding assay, respectively. Cocaine (10-8 -10-3 M) increased [Ca2+]i by up to 43% over basal level in a dose dependent manner. Norepinephrine (NE) also elevated [Ca2+]i in a dose dependent mode (202% over basal level at 10-4 M). However, cocaine in the same concentration range did not augment NE-evoked responses. Preincubation of the cells with cocaine (10-6 M, 60 sec.) increased the IP3 generation by up to 300% over basal level. Cocaine (10-6 M) also augmented NE and sodium fluoride-evoked increases in IP3 production. We conclude that contractile effect of cocaine on human myometrium can be explained, at least partially, through its stimulation of G protein-phospholipase C system with generation of IP3 and subsequent release of calcium from IP3-controlled cellular stores.
  • Authors

    Published In

  • The FASEB Journal  Journal
  • Author List

  • Fomin VP; Natarajan V; Singh D; Brown HL; Hurd WW
  • Volume

  • 12
  • Issue

  • 5