RT Journal Article
SR Electronic
T1 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
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 1357
OP 1365
VO 280
IS 3
A1 Daniela Dumitriu
A1 Stéphane Prié
A1 Sylvie G. Bernier
A1 Gaétan Guillemette
A1 Pierre Sirois
YR 1997
UL http://jpet.aspetjournals.org/content/280/3/1357.abstract
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