Cerastatin, a new potent inhibitor of platelet aggregation from the venom of the Tunisian viper, Cerastes cerastes.
Cerastatin, a potent platelet aggregation inhibitor, was purified by gel filtration on Sephadex G-75, followed by two ion exchange chromatographies on Mono-S columns. Cerastatin is a neutral glycoprotein (pI = 6.2) of 32 kDa, made up of at least three subunits. It is devoid of phospholipase A2, esterase, fibrinogenolytic and amidolytic activities. It inhibits aggregation of washed platelets, induced by either collagen, PAF acether or thrombin, with similar IC50 of 2.3 nM. Cerastatin also inhibits the thrombin-induced clot retraction of platelet-rich plasma. It does not inhibit the amidolytic or the procoagulant activities of thrombin Cerastatin caused no lytic effect on platelet membranes since it did not cause release of lactate dehydrogenase. Pretreatment of platelets with cerastatin irreversibly inhibits the aggregation induced by thrombin. Also cerastatin completely inhibits the fibrinogen-induced aggregation of alpha chymotrypsin-treated platelets. Cerastatin therefore inhibits platelet aggregation by interfering with the interaction of fibrinogen with fibrinogen receptors.
Marrakchi
N
N
Laboratoire des Venins et Toxines, Institut Pasteur de Tunis.
Barbouche
R
R
Bon
C
C
el Ayeb
M
M
D000818:Animals; D002918:Chymotrypsin / Q000494:pharmacology; D003018:Clot Retraction; D005260:Female; D006023:Glycoproteins / Q000737:chemistry / Q000302:isolation & purification / Q000633:toxicity*; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000633:toxicity*; D011817:Rabbits; D014757:Viper Venoms / Q000737:chemistry / Q000302:isolation & purification / Q000633:toxicity*
D006023:Glycoproteins; D010975:Platelet Aggregation Inhibitors; D014757:Viper Venoms; C105820:cerastatin protein, Cerastes cerastes; D002918:Chymotrypsin