A synthetic peptide derived from the sequence of a type I collagen receptor inhibits type collagen-mediated platelet aggregation

A synthetic peptide-1, an 18 amino acid residue peptide derived from a hydrophilic domain of a cloned platelet type I collagen receptor, was used to study the role of the receptor on types I and III collagen-induced platelet aggregation and the release of ATP. The peptide inhibits the type I, but not the type III, collagen-induced platelet aggregation and the release of ATP in a dose-dependent manner. The [I-125]peptide-1 specifically binds to type I collagen-coated microtiter wells in a dose-dependent manner (with K-d = 10 nM). The binding of [I-125]peptide-1 can be inhibited by an excess of unlabeled peptide-1 suggesting that the binding is specific. The labeled peptide-1 does not bind to type III collagen-coated microtiter wells, Results from an enzyme-linked immunosorbent assay show that the peptide reacts with the poly-and monoclonal antibodies raised against the purified platelet type I collagen receptor (M-r 65 kD). The peptide also inhibits the adhesion of platelets on type I collagen matrix and rabbit aortic segments in a dose-dependent manner. These results suggest that the reactive. site of the platelet receptor for type I collagen resides in this portion of the molecule.