Convulxin (Cx), a component of the
venom of the snake Crotalus durissus cascavella, induced the concentration-dependent aggregation of guinea-pig platelets when used at and above 50 +/- 5 ng/ml, accompanied by the release of
ATP and by the formation of
thromboxanes (Tx). Platelet activation by Cx was not due to potential contaminants found in the crude
snake venom, such as
phospholipase A2 and clotting
enzymes.
Aspirin (50-100 microM) failed to interfere with the platelet effects of Cx, demonstrating independence from
cyclo-oxygenase. In contrast,
indomethacin (50 microM) displayed a distinct inhibitory activity on the effects of Cx, as compared to
aspirin, and thus exerts
cyclo-oxygenase-independent effects on platelet activation. The
ADP scavenger
creatine phosphate/
creatine phosphokinase (CP/CPK) inhibited aggregation by Cx used at concentrations below 6-8 times the threshold, but failed to interfere with higher amounts. Platelet aggregation by Cx was inhibited and reversed once established by
EDTA (5mM) and by
prostacyclin (0.1-1 microM). Cx-induced activation of platelets is thus Ca2+-dependent and liable to control by the
adenylate cyclase-
cyclic AMP system.
Convulxin induced hypotension, bronchoconstriction and
thrombocytopenia when injected i.v. to the anesthetised guinea pig at 0.3-3 microgram/kg.
Aspirin and
indomethacin (20 and 5 mg/kg respectively)
mepyramine and
methysergide (02. mg/kg) failed to interfere with these effects, but the combination of either
aspirin or
indomethacin with
methysergide and
mepyramine, suppressed the bronchial effects of Cx, leaving the hypotensive and thrombopenic effects unchanged. This synergism remains unexplained. Bronchoconstriction was platelet-dependent, being suppressed by platelet depletion with antiplatelet serum or by i.v.
prostacyclin (1-10 microgram/kg).