Fibrinogenolytic properties of natrahagin (a proteinase from cobra venom) and its effect on human platelet aggregation.
OBJECTIVE
To study the fibrinogenolytic properties of natrahagin and its effect on platelet aggregation.


METHODS
SDS-PAGE, fibrinogenolytic activity assay, platelet aggregation.


RESULTS
Upon incubation of fibrinogen with natrahagin at the ratio of 50:1 (w/w), A alpha-chains of fibrinogen were almost completely hydrolyzed in 5 min; however, at least 6 h was needed for the complete degradation of gamma-chains. Fibrinogenolytic activity of natrahagin was 0.349 +/- 0.044 g.min-1.g-1 as determined by its ability to reduce the clottable fibrinogen. On the other hand, natrahagin concentration-dependently inhibited platelet aggregation induced by ristocetin in platelet-rich plasma and thrombin (80 U.L-1) in washed platelets with IC50 (95% confidence limit) of 56 (40-79) and 3.3 (1.4-8.0) mg.L-1. No inhibitory effect was found on collagen- and ADP-induced platelet aggregation even when the dose of natrahagin reached 200 mg.L-1.


CONCLUSIONS
Natrahagin is an alpha, gamma-fibrinogenase with an inhibitory effect on platelet membrane glycoprotein Ib (GPIb)-dependent platelet aggregation.
Institute of Pharmaceutical Sciences, First Military Medical University, Guangzhou 510515, China.
Z G
ZG
Zhu
S G
SG
Wu
D000328:Adult; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004546:Elapid Venoms / Q000737:chemistry; D005340:Fibrinogen / Q000378:metabolism; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008666:Metalloendopeptidases / Q000494:pharmacology*; D010634:Phenobarbital / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011802:Quinidine / Q000494:pharmacology*
D004338:Drug Combinations; D004546:Elapid Venoms; D005343:Fibrinolytic Agents; D010975:Platelet Aggregation Inhibitors; D005340:Fibrinogen; D008666:Metalloendopeptidases; C424242:natrahagin; D011802:Quinidine; C033457:phenobarbital quinidine; D010634:Phenobarbital