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Antiplatelet protease, kistomin, selectively cleaves human platelet glycoprotein Ib.
- Source :
-
Biochimica et biophysica acta [Biochim Biophys Acta] 1993 Nov 28; Vol. 1158 (3), pp. 293-9. - Publication Year :
- 1993
-
Abstract
- Kistomin, a metalloprotease purified from venom of Calloselasma rhodostoma, dose- and time-dependently prolonged the latent period of aggregation and inhibited ATP secretion of human washed platelets stimulated by thrombin. It inhibited aggregation induced by low concentrations of thrombin (< or = 0.2 U/ml) whereas it had only slight effect on aggregation induced by high concentrations of thrombin (> or = 0.5 U/ml). Meanwhile it also inhibited ristocetin-induced platelet aggregation in a dose- and time-dependent manner. It significantly inhibited cytosolic calcium rise of Quin 2--loaded platelets, completely blocked thromboxane B2 formation, and blocked [3H]inositol phosphates formation of [3H]myoinositol loaded platelets stimulated by 0.1 U/ml of thrombin. Kistomin inhibited significantly thromboxane but not [3H]inositol phosphates formation of platelets stimulated by a high concentration of thrombin (1 U/ml). Incubation of platelets with kistomin resulted in a selective cleavage of platelet membrane glycoprotein Ib as revealed by SDS/PAGE stained by periodic acid/Schiff reagent. These results suggested that thrombin activates platelets at least through two receptors/or effectors-mediated events. In addition to glycoprotein Ib, other surface membrane component(s) (e.g., the seven transmembrane domain thrombin receptor) may also be important in regulating the biochemical events of human platelets in response to thrombin. However, the extent and rate of platelet aggregation stimulated by low concentrations of thrombin ( < or = 0.2 U/ml) are closely related with the intactness of glycoprotein Ib.
- Subjects :
- Calcium analysis
Cell Membrane drug effects
Humans
Inositol Phosphates analysis
Metalloendopeptidases isolation & purification
Phospholipases A metabolism
Platelet Aggregation drug effects
Platelet Membrane Glycoproteins isolation & purification
Thrombin antagonists & inhibitors
Thromboxane B2 biosynthesis
Type C Phospholipases metabolism
Ancrod pharmacology
Metalloendopeptidases pharmacology
Platelet Aggregation Inhibitors pharmacology
Platelet Membrane Glycoproteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0006-3002
- Volume :
- 1158
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Biochimica et biophysica acta
- Publication Type :
- Academic Journal
- Accession number :
- 8251530
- Full Text :
- https://doi.org/10.1016/0304-4165(93)90028-7