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Effect of Formosn cobra (Naja naja atra ) venom phospholipase A2 on platelet aggregation and blood coagulation
168
THROMBOSIS RESEARCH
Suppl . VI,
1986
330 EFFECT OF FORMOSNCOBRA (NAJA MAJA I\TRA) VENOMPHOSPIIOLIPASEA ON PLATELET Teng, Y.P. Kuo, L.2. Lee and C. AGGREGATIONAND BLOOD C0AmTmC.M.
Pharmacological Institute, College of Medicine, Ouyang. University, Taipei, Taiwan, R.O.C.
National Taiwan
Phospholipase A2 isolated from Formosan cobra (Baja naja atra) venom induced a biuhasic effect on washed rabbit olatelets. The first vhase was a reversible aggregation which was blocked by indomethacin, mepacrine, nitroprusside, tetracaine and irnipramine. Thromboxane B2 formation induced by the venom phospholipase A, was inhibited by mepacrine, indomethacin, tetracaine or imipramine bui not by nitroprusside or PGEl. The second phase was an inhibitory effect on the aggregation induced by orachidonic acid, ADP, platelet activating factor (PAF) or collagen. This effect was dependent on the enzymatic property of the venom phospholipase A2 and mimicked those of arachidonic acid and lysophosphatidyl choline. The inhibition was more marked at low concentrations of calcium. The venom phospholipase A2 prolonged the calcium clotting time and plasma prothroinbin time and decreased the elasticity of the clot. These anticoagulant effects were potentiated by cobra cardiotoxin. It was concluded that the first stimulatory phase on platelets was due to arachidonic acid liberation from platelet membrane, while the second phase of inhibition might be due to the inhibitory actions of the split products produced by the venom phospholipase A2. The anticoagulant effect OF cobra venom was caused by the synergistic effect of both phospholipase A and cardiotoxin. 2
331 THE ROLE OF AGGREGATION AND THROMBOXANE A2 IN PLATELET ALPHA GRANULES. H. Riess, B. Reinhardt, Klinikum Gronhadern, Hiller. Medical Department II I, Munich, D 8000 Munchen 70.
THE RELEASE H. Ronft, University
OF E. of
(PDGF) is thought to play an important Platelet derived growth factor PDGF is located together with I3-thromboglobulin role in atherogenesis. (OTG) and platelet factor 4 (PF4) in platelet alpha granules. BTG and PF4 were measured by RIA when released from platelets in aggregation vitro after stimulation by collagen (lt.rg/ml) . In addition (turbidometry) was recorded and thromboxane B2 (TxB~ ) synthesis was inhibition (COI) resulted in a RIA. Cyclooxigenase estimated by decrease of OTG (58% of control), PF4 (43%) and TxB2 (11%). The same inhibition (TxSI) (BTG:50%, synthetase for thromboxane was true receptor blockade (TRB) did not TxBz :4%). Thromboxane PF4:43%, but reduced the release of OTG (53%) and PF4 inhibit TxBz production, inhibited to 50% by the antiplatelet Platelet aggregation was (50%). adenosine diphosphate (lpg/ml) to induce platelet Using drugs. did inhibit antiplatelet not and the drugs aggregation release TxSI :56%, was reduced (BTG: CO1 :61%, but release aggregation TRB:44%). Again TxBz production was decreased by CO1 or TxSI but not by TRB. We conclude that release of platelet alpha granules after stimulation antiplatelet drugs release may be triggered by thromboxane A2. Using may be reduced even when platelet aggregation is not inhibited.
THROMBOSIS RESEARCH
Suppl . VI,
1986
330 EFFECT OF FORMOSNCOBRA (NAJA MAJA I\TRA) VENOMPHOSPIIOLIPASEA ON PLATELET Teng, Y.P. Kuo, L.2. Lee and C. AGGREGATIONAND BLOOD C0AmTmC.M.
Pharmacological Institute, College of Medicine, Ouyang. University, Taipei, Taiwan, R.O.C.
National Taiwan
Phospholipase A2 isolated from Formosan cobra (Baja naja atra) venom induced a biuhasic effect on washed rabbit olatelets. The first vhase was a reversible aggregation which was blocked by indomethacin, mepacrine, nitroprusside, tetracaine and irnipramine. Thromboxane B2 formation induced by the venom phospholipase A, was inhibited by mepacrine, indomethacin, tetracaine or imipramine bui not by nitroprusside or PGEl. The second phase was an inhibitory effect on the aggregation induced by orachidonic acid, ADP, platelet activating factor (PAF) or collagen. This effect was dependent on the enzymatic property of the venom phospholipase A2 and mimicked those of arachidonic acid and lysophosphatidyl choline. The inhibition was more marked at low concentrations of calcium. The venom phospholipase A2 prolonged the calcium clotting time and plasma prothroinbin time and decreased the elasticity of the clot. These anticoagulant effects were potentiated by cobra cardiotoxin. It was concluded that the first stimulatory phase on platelets was due to arachidonic acid liberation from platelet membrane, while the second phase of inhibition might be due to the inhibitory actions of the split products produced by the venom phospholipase A2. The anticoagulant effect OF cobra venom was caused by the synergistic effect of both phospholipase A and cardiotoxin. 2
331 THE ROLE OF AGGREGATION AND THROMBOXANE A2 IN PLATELET ALPHA GRANULES. H. Riess, B. Reinhardt, Klinikum Gronhadern, Hiller. Medical Department II I, Munich, D 8000 Munchen 70.
THE RELEASE H. Ronft, University
OF E. of
(PDGF) is thought to play an important Platelet derived growth factor PDGF is located together with I3-thromboglobulin role in atherogenesis. (OTG) and platelet factor 4 (PF4) in platelet alpha granules. BTG and PF4 were measured by RIA when released from platelets in aggregation vitro after stimulation by collagen (lt.rg/ml) . In addition (turbidometry) was recorded and thromboxane B2 (TxB~ ) synthesis was inhibition (COI) resulted in a RIA. Cyclooxigenase estimated by decrease of OTG (58% of control), PF4 (43%) and TxB2 (11%). The same inhibition (TxSI) (BTG:50%, synthetase for thromboxane was true receptor blockade (TRB) did not TxBz :4%). Thromboxane PF4:43%, but reduced the release of OTG (53%) and PF4 inhibit TxBz production, inhibited to 50% by the antiplatelet Platelet aggregation was (50%). adenosine diphosphate (lpg/ml) to induce platelet Using drugs. did inhibit antiplatelet not and the drugs aggregation release TxSI :56%, was reduced (BTG: CO1 :61%, but release aggregation TRB:44%). Again TxBz production was decreased by CO1 or TxSI but not by TRB. We conclude that release of platelet alpha granules after stimulation antiplatelet drugs release may be triggered by thromboxane A2. Using may be reduced even when platelet aggregation is not inhibited.