Identification and characterization of a collagen-induced platelet aggregation inhibitor, triplatin, from salivary glands of the assassin bug, Triatoma infestans.
To facilitate feeding, certain hematophagous invertebrates possess inhibitors of collagen-induced platelet aggregation in their saliva. However, their mechanisms of action have not been fully elucidated. Here, we describe two major salivary proteins, triplatin-1 and -2, from the assassin bug, Triatoma infestans, which inhibited platelet aggregation induced by collagen but not by other agents including ADP, arachidonic acid, U46619 and thrombin. Furthermore, these triplatins also inhibited platelet aggregation induced by collagen-related peptide, a specific agonist of the major collagen-signaling receptor glycoprotein (GP)VI. Moreover, triplatin-1 inhibited Fc receptor gamma-chain phosphorylation induced by collagen, which is the first step of GPVI-mediated signaling. These results strongly suggest that triplatins target GPVI and inhibit signal transduction necessary for platelet activation by collagen. This is the first report on the mechanism of action of collagen-induced platelet aggregation inhibitors from hematophagus invertebrates.
Morita
Akihiro
A
Department of Medical Zoology, School of Medicine, Mie University, Edobashi, Tsu, Japan.
Isawa
Haruhiko
H
Orito
Yuki
Y
Iwanaga
Shiroh
S
Chinzei
Yasuo
Y
Yuda
Masao
M
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D016718:Arachidonic Acid / Q000737:chemistry; D001792:Blood Platelets / Q000378:metabolism; D003001:Cloning, Molecular; D003094:Collagen / Q000737:chemistry*; D008969:Molecular Sequence Data; D010974:Platelet Aggregation; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D010980:Platelet Membrane Glycoproteins / Q000737:chemistry; D012463:Saliva / Q000378:metabolism; D012471:Salivary Proteins and Peptides / Q000737:chemistry* / Q000494:pharmacology; D015398:Signal Transduction; D014224:Triatoma / Q000378:metabolism*
D010975:Platelet Aggregation Inhibitors; D010980:Platelet Membrane Glycoproteins; D012471:Salivary Proteins and Peptides; C098341:platelet membrane glycoprotein VI; C512458:triplatin, Triatoma infestans; D016718:Arachidonic Acid; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D003094:Collagen