Role of nitric oxide synthase in collagen-platelet interaction: involvement of platelet nonintegrin collagen receptor nitrotyrosylation.
Platelets possess the endothelial isoform of nitric oxide synthase (eNOS), which plays an important role in platelet function. Other laboratories, including ours, have reported that nitric oxide (NO) is released upon exposure of platelets to collagen, but the mechanism of the interaction is not yet established. The objective of this study is to examine the possible role of nonintegrin receptor nitrotyrosylation on collagen-induced platelet aggregation. Results of the study show that two platelet proteins with M(r) of 65- and 23-kDa proteins are nitrotyrosylated in a time-dependent manner after the addition of type I collagen. The M(r) 65-kDa protein is identified as the platelet receptor for type I collagen. The recombinant protein of the platelet receptor for type I collagen can also be nitrotyrosylated. The nitrotyrosylated recombinant protein loses its ability to inhibit type I collagen-induced platelet aggregation. In addition, the polyclonal anti-65 kDa immunoprecipitates eNOS suggesting that the platelet nonintegrin receptor for type I collagen is closely linked to the eNOS. These results demonstrate that the inhibitory effect of NO on collagen-induced platelet aggregation may be mediated by the nitrotyrosylation of the 65-kDa receptor.
Chiang
T M
TM
Veterans Affairs Medical Center and the Department of Medicine, University of Tennessee-Memphis, Memphis, TN 38104, USA. tchiang@utmem2.utmem.edu
Cole
F
F
Woo-Rasberry
V
V
Kang
E S
ES
D001792:Blood Platelets / Q000502:physiology*; D001798:Blood Proteins / Q000378:metabolism*; D003094:Collagen / Q000494:pharmacology / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D016023:Integrins / Q000097:blood*; D007700:Kinetics; D008970:Molecular Weight; D009569:Nitric Oxide / Q000097:blood; D019001:Nitric Oxide Synthase / Q000097:blood*; D052250:Nitric Oxide Synthase Type III; D010920:Placenta; D010974:Platelet Aggregation / Q000187:drug effects / Q000502:physiology*; D038981:Receptors, Collagen; D011994:Recombinant Proteins / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000097:blood*
D001798:Blood Proteins; D016023:Integrins; D038981:Receptors, Collagen; D011994:Recombinant Proteins; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine; D003094:Collagen; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III