Antagonism of the platelet activating factor-induced rise of the intracellular XXXX ion concentration of U937 cells.

@entity1 @entity8285 @entity6849 @entity6848 @entity593 @entity1360 @entity460 @entity3766 @entity141 @entity5567
1. U937 cells are a continuous line of @entity1 cells of committed monocytic origin which serve as a useful model for studying @entity1 monocytic function. The present study investigated the effect of platelet-activating factor (Paf) on intracellular free @entity460 ion concentration ([ @entity141 ]i) in U937 cells using the @entity460 fluorescent probe @entity593 . 2. The naturally-occurring stereoisomer (R)- @entity5567 (0.01-300 nM) and the stable, less hydrolysable racemic Paf analogue PR1501 (10 nM-3 microM) produced dose-related and rapid elevations of 100-1200 nM [ @entity141 ]i above a basal value of 135 +/- 9 nM (n = 22). 3. The unnatural stereoisomer (S)-Paf and the natural stereoisomer lyso-(R)-Paf had no effect on basal [ @entity141 ]i at 30 microM, approximately 100,000 times the concentration found to be the threshold concentration to elicit a response to (R)-Paf. 4. @entity8285 (LTB4) also induced increases in [ @entity141 ]i in the concentration range 28.5 nM-2.85 microM but the responses were smaller and of shorter duration than those induced by Paf. 5. Five compounds, @entity6849 , Ro 19-3704, L-652,731, @entity3766 , and @entity6848 , inhibited suboptimal Paf (10 nM)-induced increase in [ @entity141 ]i with IC50s of 48 +/- 2, 118 +/- 33, 318 +/- 131, 340 +/- 205 and 2320 +/- 183 nM 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 microM had no effect upon the increased [ @entity141 ]i induced by either LTB4 or the @entity460 ionophore, @entity1360 . 7. These results suggest that U937 cells respond to Paf at least with respect to elevated [ @entity141 ]i as measured by @entity593 and that these cells may well possess a Paf receptor as suggested by the action of specific antagonists and the stereoselectivity observed with Paf.
