Thrombosis and Haemostasis, Inhaltsverzeichnis Thromb Haemost 1989; 61(02): 183-188DOI: 10.1055/s-0038-1646556 Original Article Schattauer GmbH Stuttgart Demonstration of Ac-Arg-Gly-Asp-Ser-NH2 as an Antiaggregatory Agent in the Dog by Intracoronary Administration R J Shebuski 1 The Department of Pharmacology, Smith Kline & French Laboratories, King of Prussia, PA, USA , D E Berry 2 The Department of Biomolecular Discovery, Smith Kline & French Laboratories, King of Prussia, PA, USA , D B Bennett 2 The Department of Biomolecular Discovery, Smith Kline & French Laboratories, King of Prussia, PA, USA , T Romoff 3 The Department of Peptide Chemistry, Smith Kline & French Laboratories, King of Prussia, PA, USA , B L Storer 1 The Department of Pharmacology, Smith Kline & French Laboratories, King of Prussia, PA, USA , F Ali 3 The Department of Peptide Chemistry, Smith Kline & French Laboratories, King of Prussia, PA, USA , J Samanen 3 The Department of Peptide Chemistry, Smith Kline & French Laboratories, King of Prussia, PA, USA › Institutsangaben Artikel empfehlen Abstract als PDF herunterladen Artikel einzeln kaufen Summary 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which is a peptide fragment from fibrinogen to Ac-RGES-NH2 in which the aspartic acid (D) of Ac-RGDS-NH2 has been replaced by glutamic acid (E).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-NHz otr 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. Keywords KeywordsFibrinogen receptor antagonists - Platelet aggregation - Ac-RGDS-NH2 - Coronary artery - Canine PDF (331 kb) Referenzen References 1 Plow EF, Marguerie G, Ginsberg M. Fibrinogen, fibrinogen receptors, and the peptides that inhibit these interactions. Biochem Pharmacol 1987; 36: 4035-4040 2 Plow EF, Srouji AH, Meyer D, Marguerie G, Ginsberg MH. Evidence that three adhesive proteins interact with a common recognition site on activated platelets. J Biol Chem 1984; 259: 5388-5391 3 Gartner TK, Bennett JS. The tetrapeptide analogue of the cell attachment site of fibronectin inhibits platelet aggregation and fibrinogen binding to activated platelets. J Biol Chem 1985; 260: 11891-11894 4 Kloczewiak M, Timmons S, Lukas TJ, Hawiger J. Platelet receptor recognition site on human fibrinogen. Synthesis and structure- function relationship of peptides corresponding to the carboxy- terminal segment of the a chain Biochemistry 1984; 23: 1767-1774 5 Strong DD, Moore M, Cottrell BA, Bohonus VL, Pontes M, Evans B, Riley M, Doolittle RF. Lamprey fibrinogen γ chain: cloning, cDNA sequencing, and general characterization. Biochemistry 1985; 24: 92-101 6 Ruggeri ZM, Houghten RA, Russell SA, Zimmerman TS. Inhibition of platelet function with synthetic peptides designed to be high-affinity antagonists of fibrinogen binding to platelets. Proc Natl Acad Sci USA 1986; 83: 5708-5712 7 Plow EF, Pierschbacher MD, Ruoslahti E, Marguerie G, Ginsberg MH. Arginyl-glycyl-aspartic acid sequences and fibrinogen binding to platelets. Blood 1987; 70: 110-115 8 Plow EF, Pierschbacher MD, Ruoslahti E, Marguerie GA, Ginsberg MH. The effect of Arg-Gly-Asp-containing peptides on fibrinogen and von Willebrand factor binding to platelets. Proc Natl Acad Sci USA 1985; 81: 8057-8061 9 Gartner TK, Power JW, Beachey EH, Bennett JS, Shattil SJ. The tetrapeptide analogue of the alpha chain and decapeptide analogue of the gamma chain of fibrinogen bind to different sites on the platelet fibrinogen receptor. Blood 1987; 66 Suppl (Suppl. 01) 305 a 10 Harfenist EJ, Packham MA, Mustard JF. Effects of the cell adhesion peptide, Arg-Gly-Asp-Ser, on responses of washed platelets from human, rabbits and rats. Blood 1988; 71: 132-136 11 Stewart JM, Young JD. Solid Phase Peptide Synthesis, Second Edition. Pierce Chemical Company; Rockford, Ill: 1984: 1-139 12 Folts JD, Crowell ED, Rowe GG. Platelet aggregation in partially obstructed vessels and its elimination with aspirin. Circulation 1976; 54: 365-370 13 Aiken JW, Gorman RR, Shebuski RJ. Prevention of blockage of partially obstructed coronary arteries with prostacyclin correlates with’inhibition of platelet aggregation. Prostaglandins 1979; a 17: 483-494 14 Aiken JW, Gorman RR, Shebuski RJ. Prostacyclin prevents blockage of partially obstructed coronary arteries. In: Prostacyclin. Vane JR. Bergstrom (eds) Raven Press; New York: 1979. pp 311-321 15 Gallagher KP, Folts JD, Rowe GG. Comparison of coronary arteriograms with direct measurements of stenosed coronary arteries in dogs. Am Heart J 1978; 95: 338-347 16 Coller BS, Scudder LE. Inhibition of dog platelet function by in vivo infusion of F(ab’)2fragments of a monoclonal antibody to the platelet glycoprotein IIb/IIIa receptor. Blood 1985; 66: 1456-1459 17 Coller BS, Folts JD, Scudder LE, Smith SR. Antithrombotic effect of a monoclonal antibody to the platelet glycoprotein IIb/IIIa receptor in an experimental animal model. Blood 1986; 68: 783-786 18 Takami H, Nichols WL, Kaese SE, Bowie EJ W. Infusion study of monoclonal antibodies against porcine platelet membrane GP lb and GP IIb/IIIa: Differential effect on platelet function and bleeding time. Blood 1987; 70 Suppl (Suppl. 01) 344 a 19 Hanson SR, Pareti FI, Ruggeri ZM, Marzc UM, Kunicki TJ, Montgomery RR, Zimmerman TS, Harker LA. Effects of monoclonal antibodies against the platelet glycoprotein IIb/IIIa complex on thrombosis and hemostasis in the baboon. J Clin Invest 1988; 81: 149-158 20 Yasuda T, Gold HK, Leinbach RC, Kanke M, Fallon J, Scudder LE, Coller BS. A monoclonal antiplatelet antibody prevents acute coronary reocclusion (RO) following thrombolysis in dogs despite residual high-grade stenosis. Clin Res 1986; 34: 634 a 21 Gold HK, Coller B, Yasuda T, Saito T, Leinbach RC, Fallon JT, Ziskind AA, Guerrero L, Collen D. A monoclonal antibody to the platelet receptor GP IIb/IIIa (7E3) accelerates thrombolysis with recombinant tissue-type plasminogen activator and prevents coronary reocclusion. Circulation 1988; 77: 670-677 22 Torem S, Schneider PA, Hanson SR. Monoclonal antibody-induced inhibition of platelet function: Effects on hemostasis and vascular graft thrombosis in baboons. J Vase Surg 1988; 7: 172-180 23 Coller BS, Peerschke EI, Scudder LE, Sullivan CA. A murine monoclonal antibody that completely blocks the binding of fibrinogen to platelets produces a thrombesthenic-like state in normal platelets and binds to glycoproteins IIb and/or IIIa. J Clin Invest 1983; 72: 325-338 24 Aiken JW. Contribution of endogenous prostacyclin in control of platelet-vessel wall interaction. In: Interactions of Platelets with the Vessel Wall Oates JA, Hawiger J, Ross R. (eds) Am Physiol Soc 1985; pp 82-84 25 Hawiger J, Graber SE, Timmons S. Prostacyclin regulation of platelet receptors for adhesive macromolecules. In: Interaction of Platelets with the Vessel Wall Oates JA, Hawiger J, Ross R. (eds) Am Physiol Soc 1985; pp 89-102 26 Samanen J. Biomedical polypeptides - A wellspring of pharmaceuticals. In: Bioactive Polymeric Systems. Gebelein CG, Carraher Jr CE. (eds) Plenum; New York: 1985. pp 279-382
