Inhibition of phospholipase A2 by tiaramide in rabbit platelets. 
The mechanism by which tiaramide inhibited platelet aggregation was investigated using phospholipid labelling techniques by 14C-arachidonic acid (AA) and thin-layer chromatography.  Tiaramide did not affect cyclo-oxygenase nor thromboxane synthetase, because TXB2 was detected in tiaramide-treated platelets, unlike aspirin-treated ones, and PGE2 and PGD2 did not increase, unlike in platelets treated with OKY-1581 (an inhibitor of thromboxane synthetase).  Total phospholipid radioactivity was 82.5% of radioactivity recovered before aggregation, and this decreased to 49.0% (n = 5, P less than 0.05) after aggregation by collagen (30 micrograms/ml).  AA radioactivity was 9.6% before aggregation and 40.0% after.  Tiaramide (100 microM) restored total phospholipid and AA levels to those before aggregation.  Tiaramide decreased the amount of AA liberated from 2-(3H-arachidonyl)phosphatidylcholine by whole platelet phospholipase A2 (PLA2).  Tiaramide at 10 microM inhibited collagen-induced aggregation, but not that by AA.  Tiaramide did not affect 45Ca-uptake by itself nor collagen-induced 45Ca-uptake from the external medium.  Tiaramide did not inhibit intracellular Ca mobilization, and it did not affect the calmodulin-dependent cyclic nucleotide phosphodiesterase of rabbit brain.  These facts suggest that tiaramide inhibits platelet PLA2 through mechanisms other than the blockade of Ca-influx and intracellular Ca mobilization or antagonism to calmodulin.