PT  - JOURNAL ARTICLE
AU  - Daniela Dumitriu
AU  - Stéphane Prié
AU  - Sylvie G. Bernier
AU  - Gaétan Guillemette
AU  - Pierre Sirois
TI  - Mechanism of Action of Leukotriene D<sub>4</sub> on Guinea Pig Tracheal Smooth Muscle Cells: Roles of Ca<sup>++</sup> Influx and Intracellular Ca<sup>++</sup> Release
DP  - 1997 Mar 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 1357--1365
VI  - 280
IP  - 3
4099  - http://jpet.aspetjournals.org/content/280/3/1357.short
4100  - http://jpet.aspetjournals.org/content/280/3/1357.full
SO  - J Pharmacol Exp Ther1997 Mar 01; 280
AB  - The effects of leukotriene D4 (LTD4) on the concentration of intracellular cytosolic free calcium ([Ca++]i) and on phosphoinositide hydrolysis were studied in cultured guinea pig tracheal smooth muscle cells. In Fura-2-loaded cells, LTD4(10−9–10−6 M) induced concentration-dependent changes in [Ca++]iconsisting of a slow, transient increase followed by a sustained phase. Preincubation of cells with LTD4 receptor antagonist MK-571 (10−6 M) blocked the increase in [Ca++]i. Similarly, LTD4-induced inositol phosphate ([3H]InsPs) synthesis was transient, concentration-dependent and inhibited by the LTD4 antagonist. In the absence of extracellular Ca++, LTD4 failed to induce [Ca++]i increases and [3H]InsPs formation. Accordingly, NiCl2 completely inhibited the LTD4-stimulated [3H]InsPs synthesis. Nifedipine (10−5 M) had a slight inhibitory effect on [Ca++]i increase but significantly reduced (40–50%) the [3H]InsPs accumulation. These findings indicate that LTD4-stimulated inositol phosphate synthesis and [Ca++]i increases in tracheal smooth muscle cells are receptor-mediated events and are dependent on the availability of extracellular Ca++. It is suggested that Ca++ influx plays a major role in the LTD4signal transduction mechanism. The American Society for Pharmacology and Experimental Therapeutics