Phospholipase A2 activity in platelets of patients with uremia.
Platelets of patients with uremia develop a defective platelet function and have a decreased production of thromboxane B2 (TxB2). Activated platelets generate thromboxane from free arachidonate that is previously released from the membrane phospholipids (PLs) by phospholipases. Phospholipase A2 (PLA2) release up to 70% of the arachidonate in normal platelets, and to date, the activity of this enzyme in uremia is unknown. This work studied the PLA2 activity in the platelets of nine uremic patients and nine healthy volunteers. Washed platelets were labelled with [(14)C]arachidonic acid and activated with calcium ionophore A-23187 (4 microgr/ml). Lipids were resolved by TLC and identified by autoradiography. The distribution of [(14)C]arachidonic acid in the five major platelet phospholipids was found to be normal. Uremic platelets released more radioactivity than normal platelets (19.0 +/- 5.2% versus 11.3 +/- 1.6%, P = 0.001). The production of both, radioactive thromboxane B2 and hydroxyheptadecatrienoic acid was normal (2.6 +/- 1.2% and 3.5 +/- 1.6% of total radioactivity respectively), but the formation of the lipoxygenase metabolite hydroxyeicosatetraenoic acid was increased with respect to the controls (12.9 +/- 4.6% vs 7.0 +/- 1.3% of total radioactivity, P = 0002). In conclusion, platelets of patients with uremia have an increased activity of phospholipase A2 and produce increased amounts of hydroxyeicosatetraenoic acid, an inhibitor of the platelet function.
Vecino
Ana M
AM
Department of Haematology, Hospital Ramón y Cajal, Madrid, Spain.
Teruel
José L
JL
Navarro
José L
JL
Cesar
Jesús M
JM
D016718:Arachidonic Acid / Q000378:metabolism; D001792:Blood Platelets / Q000201:enzymology*; D000001:Calcimycin / Q000494:pharmacology; D016022:Case-Control Studies; D005231:Fatty Acids, Unsaturated / Q000096:biosynthesis; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood / Q000201:enzymology; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D010979:Platelet Function Tests; D013929:Thromboxane B2 / Q000096:biosynthesis; D014511:Uremia / Q000097:blood* / Q000201:enzymology
D005231:Fatty Acids, Unsaturated; D016718:Arachidonic Acid; D000001:Calcimycin; C008033:12-hydroxy-5,8,10-heptadecatrienoic acid; D013929:Thromboxane B2; D010741:Phospholipases A; D054467:Phospholipases A2