title: Demonstration of Ac-Arg-Gly-Asp-Ser-NH2 as an antiaggregatory agent in the dog by intracoronary administration.
abstract: This study compared the anti-platelet effect of Ac-RGDS-NH2 which is a peptide fragment from fibrinogen to Ac-RGES-NH2 in which the aspartic acid (D) of Ac-RGDS-NH2 has been replaced by glutamic acid (E). When Ac-RGDS-NH2 was infused intracoronary at concentrations of 100-400 mM, acute platelet-dependent thrombus formation in the dog coronary artery was inhibited. However, infusion of Ac-RGES-NH2 intracoronary at similar concentrations to Ac-RGDS-NH2 failed to inhibit platelet-dependent thrombus formation in the dog. Ac-RGDS-NH2 and Ac-RGES-NH2 were also tested for their ability to inhibit collagen-induced platelet aggregation in vitro. Ac-RGDS-NH2 elicited concentration-dependent inhibition of collagen-induced aggregation with no effect of Ac-RGES-NH2 on collagen-induced platelet aggregation. Thus, Ac-RGDS-NH2 is an effective antiplatelet agent after intracoronary administration in the dog and also inhibits collagen-induced platelet aggregation in vitro. Ac-RGDS-NH2 is a specific inhibitor of platelet aggregation as replacement of the aspartic acid in Ac-RGDS-NH2 with glutamic acid results in complete loss of biological activity.
authors.affiliation: Department of Pharmacology, Smith Kline & French Laboratories, King of Prussia, PA.
authors.forename: R J
authors.initials: RJ
authors.lastname: Shebuski
authors.forename: D E
authors.initials: DE
authors.lastname: Berry
authors.forename: D B
authors.initials: DB
authors.lastname: Bennett
authors.forename: T
authors.initials: T
authors.lastname: Romoff
authors.forename: B L
authors.initials: BL
authors.lastname: Storer
authors.forename: F
authors.initials: F
authors.lastname: Ali
authors.forename: J
authors.initials: J
authors.lastname: Samanen
mesh_terms: D000818:Animals; D004285:Dogs; D005260:Female; D007261:Infusions, Intra-Arterial; D008297:Male; D009842:Oligopeptides / Q000008:administration & dosage / Q000494:pharmacology*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D009842:Oligopeptides; D010975:Platelet Aggregation Inhibitors; C060414:acetyl-arginyl-glycyl-aspartyl-serinamide