European Journal of Pharmacology, 153 (1988) 231-238 231 Elsevier EJP 50410 Effect of fibrinopeptides A and B on human and rat platelet aggregation in vitro Philip K. Moore *, Isa Hussaini and Renu Bhardwaj Department of Pharmacology, King's College(KQC), Universityof London, Manresa Road, London S I4:3 6LX, U.K. Received 31 December 1987, revised MS received 26 April 1988, accepted 7 June 1988 The effect of fibrinopeptides on platelet aggregation is reported. Fibrinopeptide A (minimal effective concentra- tion, 0.65 /xM) aggregated human (but not rat) platelets suspended in plasma and at lower concentrations (0.01-0.1 /~M) potentiated platelet aggregation due to ADP and collagen in both species. Fibrinogen mimicked these effects of fibrinopeptide A. P-bromophenacyl bromide (100 ~M), mepacrine (10/xM), indomethacin (10 ttM) and dazoxiben (10 /xM) inhibited human platelet aggregation induced by fibrinopeptide A and fibrinogen. In both species, fibrinopeptide B (0.65-6.5 /~M) antagonised the platelet inhibitory effect of PGI 2 and PGD 2 but not adenosine. Antagonism was non-competitive in nature. The concentration of fibrinopeptide A required to potentiate platelet aggregation occurs naturally in the plasma of patients with thrombotic disease suggesting this effect may be of physiological significance during the formation of a thrombus. The novel action of fibrinopeptide B to reduce the platelet inhibitory effect of PGI 2 and PGD 2 may also contribute to the control of thrombus formation. Fibrinopeptides; Fibrinogen; Platelets; (Human, Rat) 1. Introduction Thrombin-induced proteolysis of fibrinogen which occurs as a natural consequence of haemos- tasis, thrombosis or inflammation, results in the sequential formation of fibrinopeptide A and fibrinopeptide B (Blomback and Vestermark, 1958). These peptides contain 16 and 14 amino acids respectively and occur naturally in the plasma of healthy humans (Nossel et al., 1974). Surprisingly, there have been few reports of the pharmacological effects of fibrinopeptides. Fibrinopeptide B has been shown to increase rat blood pressure following intravenous injection (Osbahr et al., 1967), constrict the pulmonary vascular circulation in rabbits, dogs and lambs (Bayley et al., 1967), potentiate the contractile * To whom all correspondenceshould be addressed. effect of bradykinin on the isolated rat uterus (Gladner et al., 1963) and exhibit chemotactic activity for neutrophils (Richardson et al., 1976). Since fibrinopeptides A and B are generated dur- ing coagulation of blood it is of interest to de- termine their action on other aspects of cardio- vascular haemostasis and to compare their biologi- cal activity with that of fibrinogen. In this paper we report some novel actions of these fibrinopep- tides on human and rat platelet aggregation in vitro. 2. Materials and methods 2.1. Collection of blood and preparation of plasma Blood was obtained by venepuncture of human volunteers who had not ingested aspirin-like drugs in the previous 10 days or, alternatively, by cardiac 0014-2999/88/$03.50 © 1988 Elsevier Science Publishers B.V. (Biomedical Division)