Abstract: | The metabolism of linoleic acid by washed human platelets was investigated. 1.14C linoleic acid was converted to 1.14C hydroxy octadecadienoic acids (HODES) at about the same rate with which 1.14C 12-HETE was produced from 1.14C arachidonic acid. The total radioactivity in HODEs was distributed among two isomers: 13-HODE (85%) and 9-HODE (15%) as defined by GC-MS. The production of HODES by intact washed platelets was inhibited by indomethacin (IC50:5×10−7M) which suggest that hydroxy fatty acids were produced by PGH-synthase. By contrast, the production of HODEs by platelet cytosolic fractions was not modified under indomethacin treatment but completely abolished by NDGA (10−3M) and inhibited by the platelet lipoxygenase inhibitors 15-HETE (2.10−5M) and baicalein (10−5M). Platelets thus contain two different active systems which may convert linoleic acid to hydroxy fatty acids. Since these compounds remained essentially associated with the platelets, their presence may significantly participate in the mechanisms of platelet activation. |