Effect of cocaine on cytoplasmic calcium and IP3 production in human myometrial cells
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.
Fomin, VP; Natarajan, V; Singh, D; Brown, HL; Hurd, WW
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