Agkistrodon piscivorus piscivorus platelet aggregation inhibitor: a potent inhibitor of platelet activation
| Autor: | E P Chow, B Savage, U M Marzec, Betty H. Chao, Laurence A. Harker, John M. Maraganore, J A Jakubowski |
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| Rok vydání: | 1989 |
| Předmět: |
Blood Platelets
Molecular Sequence Data Peptide Arachidonic Acids Phospholipases A Thromboxane A2 chemistry.chemical_compound Thrombin Sequence Homology Nucleic Acid Water moccasin Crotalid Venoms medicine Animals Humans Platelet Amino Acid Sequence Platelet activation chemistry.chemical_classification Arachidonic Acid Multidisciplinary Edman degradation Chemistry Platelet Activation Adenosine Diphosphate Biochemistry Phospholipases Platelet aggregation inhibitor Collagen Platelet Aggregation Inhibitors Research Article Protein Binding medicine.drug |
| Zdroj: | Proceedings of the National Academy of Sciences. 86:8050-8054 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.86.20.8050 |
| Popis: | Applaggin (Agkistrodon piscivorus piscivorus platelet aggregation inhibitor) is a potent inhibitor of platelet activation. The protein is isolated from the venom of the North American water moccasin snake in three steps, including gel filtration, cation exchange, and reverse-phase HPLC procedures. The purified protein migrates as a 17,700-Da polypeptide by SDS/PAGE under nonreducing conditions and as a 9800-Da peptide in the presence of thiol. The behavior of applaggin on SDS/PAGE would indicate that the protein is a disulfide-linked dimer. Applaggin has been completely sequenced by Edman degradation and consists of 71 amino acids. The sequence is rich in cysteine and contains Arg-Gly-Asp at residues 50-52. Applaggin blocks platelet aggregation induced by ADP, collagen, thrombin, or arachidonic acid with IC50 values ranging from 12 to 128 nM (0.2-2.3 micrograms/ml) depending on the agonist and its concentration. This inhibition is found to correlate with inhibition of thromboxane A2 generation and of dense granule release of serotonin. Inhibition by applaggin of serotonin release induced by ADP, gamma-thrombin, and collagen was monitored in plasma under stirred conditions with [3H]serotonin-loaded platelets, and IC50 values for inhibition are found to range from less than 10 to 145 nM. At saturating concentrations, 125I-labeled applaggin (125I-applaggin) binds to 28,500 sites per unstimulated, washed platelet with a Kd of 1.22 x 10(-7) M. Binding of 125I-applaggin to platelets is inhibited by the synthetic undecapeptide Arg8-Gly-Asp-Val at 200 microM. |
| Databáze: | OpenAIRE |
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