Open AccessInhibition of Phospholipase A2 by Tiaramide in Rabbit Platelets
Author(s) -
Shizuko Takano
Publication year - 1985
Publication title -
japanese journal of pharmacology/japanese journal of pharmacology
Language(s) - English
Resource type - Journals
eISSN - 1347-3506
pISSN - 0021-5198
DOI - 10.1254/jjp.39.307
Subject(s) - phospholipase a2 , platelet , chemistry , phospholipid , arachidonic acid , phosphatidylcholine , phospholipase , thromboxane , phospholipase c , intracellular , biochemistry , thromboxane a2 , thrombin , thromboxane b2 , medicine , enzyme , membrane , receptor
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.