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Antagonism of the platelet activating factor‐induced rise of the intracellular calcium ion concentration of U937 cells
Author(s) -
Ward S.G.,
Westwick J.
Publication year - 1988
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1988.tb11461.x
Subject(s) - platelet activating factor , leukotriene b4 , calcium , u937 cell , chemistry , intracellular , calcium in biology , platelet , basal (medicine) , leukotriene , antagonism , biological activity , endocrinology , fura 2 , biophysics , medicine , receptor , stereochemistry , biochemistry , in vitro , biology , inflammation , enzyme , cytosol , organic chemistry , asthma , insulin
1 U937 cells are a continuous line of human cells of committed monocytic origin which serve as a useful model for studying human monocytic function. The present study investigated the effect of platelet‐activating factor (Paf) on intracellular free calcium ion concentration ([Ca 2+ ] i ) in U937 cells using the calcium fluorescent probe fura‐2. 2 The naturally‐occurring stereoisomer (R)‐Paf (0.01–300 n m ) and the stable, less hydrolysable racemic Paf analogue PR1501 (10 n m ‐3 μ m ) produced dose‐related and rapid elevations of 100–1200 n m [Ca 2+ ] i above a basal value of 135 ± 9 n m ( n = 22). 3 The unnatural stereoisomer (S)‐Paf and the natural stereoisomer lyso‐(R)‐Paf had no effect on basal [Ca 2+ ] i at 30 μ m , approximately 100,000 times the concentration found to be the threshold concentration to elicit a response to (R)‐Paf. 4 Leukotriene B 4 (LTB 4 ) also induced increases in [Ca 2+ ] i in the concentration range 28.5 n m ‐2.85 μ m but the responses were smaller and of shorter duration than those induced by Paf. 5 Five compounds, WEB 2086, Ro 19–3704, L‐652,731, BN 52021, and CV 3988, inhibited sub‐optimal Paf (10 n m )‐induced increase in [Ca 2+ ] i with IC 50 s of 48 ± 2, 118 ± 33, 318 ± 131, 340 ± 205 and 2320 ± 183 n m respectively. All five compounds have previously been reported as specific Paf receptor antagonists, at least with respect to platelets. 6 The above compounds at 10 μ m * had no effect upon the increased [Ca 2+ ] i induced by either LTB 4 or the calcium ionophore, ionomycin. 7 These results suggest that U937 cells respond to Paf at least with respect to elevated [Ca 2+ ] i as measured by fura‐2 and that these cells may well possess a Paf receptor as suggested by the action of specific antagonists and the stereoselectivity observed with Paf.