Mechanism of platelet effects of cardiotoxins from Naja nigricollis crawshawii (spitting cobra) snake venom.
Four cardiotoxins isolated from Naja nigricollis crawshawii venom show inhibition of platelet aggregation when tested on whole blood aggregation in an electronic aggregometer. A similar inhibitory effect is observed by adding hemolyzed erythrocytes to whole blood before initiation of aggregation with collagen. Qualitatively, ADP-induced aggregation in whole blood appears to be different from collagen-induced aggregation in that the change in impedance is smaller than that induced by collagen. Thus, addition of ADP apparently "inhibits" collagen-induced aggregation as measured by the electronic aggregometer. Inclusion of apyrase in the aggregation cuvet stimulates the rate of aggregation initiated by collagen. The cardiotoxins lyse blood cells and release their cellular contents including ADP, AMP and other inhibitory substances, which reduce the impedance changes associated with collagen-induced aggregation. The cardiotoxins also lyse platelets coated onto the electrodes and reduce the impedance after aggregation is completed. Thus the lytic effects of these polypeptides cause an apparent inhibition of platelet aggregation in whole blood by both release of inhibitory components and removal of platelets from the electrodes. The lytic ability of these cardiotoxins can also explain the apparent "potentiation" and "aggregation" observed by previous workers using turbidometric aggregometers. Under these conditions, the cardiotoxins from N. nigricollis appear to both potentiate ADP-initiated aggregation and initiate aggregation themselves, but lysis is responsible, as shown by the release of cytoplasmic lactate dehydrogenase. Neurotoxin II from N. naja oxiana venom, although structurally homologous with cardiotoxins, does not lyse cells, nor did it show any effects on platelets.
Kini
R M
RM
Department of Biochemistry, Medical College of Virginia, Richmond 23298.
Evans
H J
HJ
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D001792:Blood Platelets / Q000187:drug effects* / Q000201:enzymology; D004179:Cobra Cardiotoxin Proteins / Q000494:pharmacology*; D004357:Drug Synergism; D004546:Elapid Venoms / Q000494:pharmacology*; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D009391:Nephelometry and Turbidimetry; D009498:Neurotoxins / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects*
D004179:Cobra Cardiotoxin Proteins; D004546:Elapid Venoms; D009498:Neurotoxins; D000244:Adenosine Diphosphate