Effects of Prostaglandins, Derivatives of Cyclic 3':5'-AMP, Theophylline, Cholinergic Agents and Colchicine on Clot Retraction in Dilute Platelet-Rich Plasma and Gel-Separated Platelet Test Systems

J. L Moake; P. L Cimo; K Widmer; D. M Peterson; J. R Gum

doi:10.1055/s-0038-1651477

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 1977; 38(02): 0420-0428
DOI: 10.1055/s-0038-1651477

Original Article

Schattauer GmbH

Effects of Prostaglandins, Derivatives of Cyclic 3':5'-AMP, Theophylline, Cholinergic Agents and Colchicine on Clot Retraction in Dilute Platelet-Rich Plasma and Gel-Separated Platelet Test Systems

J. L Moake

¹Division of Hematology, University of Texas Medical School at Houston, Houston, Texas 77030, U.S.A.

,

P. L Cimo

¹Division of Hematology, University of Texas Medical School at Houston, Houston, Texas 77030, U.S.A.

,

K Widmer

¹Division of Hematology, University of Texas Medical School at Houston, Houston, Texas 77030, U.S.A.

,

D. M Peterson

¹Division of Hematology, University of Texas Medical School at Houston, Houston, Texas 77030, U.S.A.

,

J. R Gum

¹Division of Hematology, University of Texas Medical School at Houston, Houston, Texas 77030, U.S.A.

› Institutsangaben

Abstract

Summary

In dilute suspensions of platelet-rich plasma (PRP) or gel-separated platelets (GSP), dibutyryl-cAMP (DBcAMP) and monobutyryl-cAMP inhibited platelet-mediated fibrin clot retraction in concentrations of 2–3 × 10^–6M, with complete inhibition at 1–3 × 10^–4M. Prostaglandin E₁ (PGE₁), which inhibited fibrin clot retraction in concentrations greater than 1.5–3 × 10^–8M, was a more effective inhibitor than either PGE₂ or PGF_2α. In the presence of theophylline (10^–4M), concentrations of DBcAMP, PGE₁ PGE₂ and PGF_2α necessary to inhibit fibrin clot retraction were reduced 50-fold for DBcAMP and 2.5 to 20-fold for the prostaglandins. In dilute PRP or GSP, inhibition of fibrin clot retraction does not result from inhibition of thrombin-induced platelet aggregation. Thus, compounds which increase platelet cAMP levels result in the inhibition of platelet-mediated fibrin clot retraction, and this inhibitory effect may be mediated, at least in part, through suppression of platelet contractility. Cyclic GMP, dibutyryl-cGMP and carbamylcholine-Cl (which stimulates guanylate cyclase) did not influence fibrin clot retraction, and did not prevent inhibition of fibrin clot retraction by DBcAMP and PGE?. Colchicine, in concentrations known to disrupt platelet microtubules (2.5 × 10^–6M to 2.5 x 10^–3M), had little inhibitory effect on either fibrin clot retraction or platelet (³H)-serotonin release.

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Referenzen

References
1 Bettex-Galland M, Lüscher E. F. 1960; Studies on the metabolism of human blood platelets in relation to clot retraction. Thrombosis et Diathesis Haemorrhagica 4: 178.
2 Bettex-Galland M, Lüscher E. F. 1961; Thrombosthenin — a contractile protein from thrombocytes. Its extraction from human blood platelets and some of its properties. Biochimica Biophysica Acta 49: 536.
3 CodÆ B, Robison G. A, Hartmann R. C. 1972; Studies on the role of cyclic AMP in platelet function. Annals of the New York Academy of Science 201: 477.
4 Corn M, Jackson D. P, Conley C. L. 1960; Components of blood necessary for clot retraction. Bulletin of the Johns Hopkins Hospital 107: 90.
5 deClerk F, Borgers M, deGaetano G, Vermylen J. 1975; Dissociation of clot retraction from platelet granule fusion and degranulation: an ultrastructural study of reptilase – human platelet-rich plasma clots. British Journal of Haematology 29.: 341.
6 deGaetano G, Bottechia D, Vermyilen J. 1973; Retraction of reptilase-clots in the presence of agents inducing or inhibiting the platelet adhesion-aggregation reaction. Thrombosis Research 2: 71.
7 Finlayson J. S. 1968. Chromatographic purification of fibrinogen. In: Laki K. (eds.) Fibrinogen. Marcel Dekker, Inc.; New York.: 39.
8 Goldberg N. D, O’dea R. F, Haddox M. K. 1973; Cyclic GMP. Advances in Cyclic Nucleotide Research 3: 155.
9 McDonald J. W. D, Stuart R. K. 1974; Interaction of prostaglandins E₁ and E₂ in regulation of cyclic-AMP and aggregation in human platelets: evidence for a common prostaglandin receptor. Journal of Laboratory and Clinical Medicine 84: 111.
10 Mills D. B. C, SmITh J. B. 1971; The influence on platelet aggregation of drugs that affect the accumulation of adenosine 3’:5’-cyclic monophosphate in platelets. Biochemistry 121: 185.
11 Morse E. E, Jackson D. P, Conley C. L. 1967; Effects of reptilase and thrombin on human blood platelets and observations on the molecular mechanism of clot retraction. Journal of Laboratory and Clinical Medicine 70: 106.
12 Murer E. H. 1971; a Effect of prostaglandin E1 on clot retraction. Nature 229: 112.
13 Murer E. H. 1971; b Compounds known to affect the cyclic adenosine monophosphate level in blood platelets: Effects on thrombin-induced clot retraction and platelet release. Biochimica Biophysica Acta 237: 310.
14 Niewiarowski S, Regoeczi E, Stewart G. F, Senyi A. F, Mustard J. F. 1972; Platelet interaction with polymerizing fibrin. Journal of Clinical Investigation 51: 685.
15 Niewiarowski S, Stewart G. J, Nath N, Sha A. T, Lieberman G. E. 1975; ADP, thrombin and Bothrops atrox thrombinlike enzyme in platelet-dependent fibrin reaction. American Journal of Physiology 229: 737.
16 Salzman E. W, Levine L. 1971; Cyclic 3’,5’-adenosine monophosphate in human blood platelets. II. Effect of N⁶-2’-O-dibutyryl cyclic 3’,5’-adenosine monophosphate on platelet function. Journal of Clinical Investigation 50: 131.
17 Schultz G, Hardman J. G, Sutherland E. W. 1973. Cyclic nucleotides and smooth muscle function. In: Austin K. F, Lichtenstein L. M. (eds.) Asthma: Pathology, Immunopharmacology and Treatment.. Academic Press; New York: 123.
18 Shepro D, Belamarich F. A, Chao F. C. 1969; Retardation of clot retraction after incubation of platelets with colchicine and heavy water. Nature 221: 563.
19 Weiss H. J, Tschopp T. B, Rogers J, Brand H. 1974; Studies of platelet 5-hydroxytryptamine (serotonin) in storage pool disease and albinism. Journal of Clinical Investigation 54: 421.
20 White J. G. 1968; Effects of colchicine and vinca alkaloids on human platelets. I. Influence on platelet microtubules and contractile function. American Journal of Pathology 53: 281.
21 Widmer K, Moake J. L. 1976; Clot retraction: evaluation in dilute suspensions of platelet-rich plasma and gel-separated platelets. Journal of Laboratory and Clinical Medicine 87: 49.
22 Zucker-Franklin D. 1969; Microfibrils of blood platelets: their relationship to microtubules and the contractile protein. Journal of Clinical investigation 48: 165.
23 Zurier R. B, Weismann G, Hoffstein S, Kammerman S, Tai H. H. 1974; Mechanisms of lysosomal enzyme release from human leukocytes. II. Effects of cAMP and cGMP, autonomic agonists, and agents which affect microtubule function. Journal of Clinical Investigation 53: 297.