Download PDF
Thromb Haemost 1977; 37(03): 413-422
DOI: 10.1055/s-0038-1649249
Original Article
Schattauer GmbH

Potentiation by α and Inhibition by β-Adrenergic Stimulations of Rat Platelet Aggregation

A Comparative Study with Human and Rabbit Platelets
S. K Yu   *
1   Laboratory of Experimental Pathology, Institut de Cardiologie de Montréal, and Department of Pathology, Université de Montréal, Montreal, Quebec, Canada
,
J. G Latour   **
1   Laboratory of Experimental Pathology, Institut de Cardiologie de Montréal, and Department of Pathology, Université de Montréal, Montreal, Quebec, Canada
› Author Affiliations
Further Information

Publication History

Received 30 September 1976

Accepted 25 March 1977

Publication Date:
03 July 2018 (online)

  PDF Download  Permissions and Reprints

Summary

Epinephrine, known to potentiate and elicit aggregation of human platelets, was shown to inhibit thrombin-induced aggregation of rat platelets, delaying the onset of aggregation from 2 to 12 times. Incubation of rat platelet suspensions with propranolol (1.25–30 μM), inactive by itself, totally prevented the inhibitory effect of epinephrine and also permitted a potentiation effect to show up. On the contrary, phentolamine (1.25–30 μM) potentiated the inhibitory effect of epinephrine on rat platelets and unmasked an inhibitory effect on human platelets. Finally, isoproterenol (0.25–9 μM) produced a marked inhibition of aggregation induced by thrombin, ADP and collagen in the three species studied, but most particularly in the rat. From these results, we conclude that stimulation of the platelet adrenergic receptors may either result in promotion (α-stimulation) or inhibition (β-stimulation) of platelet aggregation. Furthermore, differences in the ratios or responses of α/β receptors may account for species variations in the platelet aggregation response to catecholamine challenge.

* Fellow of the MRC of Canada.


** “Chercheur-Boursier” Conseil de la Recherche en Santé du Québec.


 

  • References

  • 1 Abdulla Y. H. Beta-adrenergic receptors in human platelets. Journal of Atherosclerosis Research 1969; 9: 171
    CrossrefPubMedGoogle Scholar
  • 2 Ardlie N. G, Packham M. A, Mustard J. F. Adenosine diphosphate-induced platelet aggregation in suspensions of washed rabbit platelets. British Journal of Haematology 1970; 19: 7
    CrossrefPubMedGoogle Scholar
  • 3 Ardlie N. G, Glew G, Schwartz C. J. Influence of catecholamines on nucleotide-induced platelet aggregation. Nature 1966; 212: 415
    CrossrefPubMedGoogle Scholar
  • 4 Aster R. M, Jandl J. H. Platelet sequestration in man. I. Method. Journal of Clinical Investigation 1964; 43: 843
    PubMedGoogle Scholar
  • 5 Ball G, Brereton G. G, Fulwood M, Ireland D. M, Yates P. Effect of prostaglandin Ei alone and in combination with theophylline or aspirin on collagen-induced platelet aggregation and on platelet nucleotides including adenosine 3’,5’ AMP. Biochemical Journal 1970; 120: 709
    CrossrefPubMedGoogle Scholar
  • 6 Brodie G. N, Baenziger N. L, Chase L. R, Majerus P. W. The effects of thrombin on adenyl cyclase activity and a membrane protein from human platelets. Journal of Clinical Investigation 1972; 51: 81
    CrossrefPubMedGoogle Scholar
  • 7 Bygdeman S, Johnsen O. Studies on the effect of adrenergic blocking drugs on catecholamine-induced platelet aggregation and uptake of noradrenaline and 5-hydroxytryptamine. Acta Physiologica Scandinavica 1969; 75: 129
    CrossrefPubMedGoogle Scholar
  • 8 Clayton S, Cross M. J. The aggregation of blood platelets by catecholamines and by thrombin. Journal of Physiology 1963; 169: 82
    PubMedGoogle Scholar
  • 9 Gibelli A, Montanari C, Bellani D, Mandelli V, Sacchetti G. Beta-blocking drugs and human platelet aggregation in vitro. Experientia 1973; 29: 186
    CrossrefPubMedGoogle Scholar
  • 10 Haslam R. J. Roles of cyclic nucleotides in platelet function. In: Biochemistry and Pharmacology of platelets. Ciba Foundation Symposium 35, Elsevier, Excerpta Medica, North Holland Co. 1975: 121
    Google Scholar
  • 11 Haslam R.J, Taylor A. Effects of catecholamines on the formation of adenosine 3’,5’cyclic AMP in human blood platelets. Biochemical Journal 1971; 125: 377
    CrossrefPubMedGoogle Scholar
  • 12 Latour J. G, Leger C. Prevention by glucocorticoids of disseminated intravascular coagulation induced by endotoxin: Mechanisms. The Journal of Laboratory and Clinical Medicine 1975; 85: 934
    PubMedGoogle Scholar
  • 13 MacMillan D. C. Secondary clumping effect in human citrated platelet-rich plasma produced by adenosine diphosphate and adrenaline. Nature 1966; 211: 140
    CrossrefPubMedGoogle Scholar
  • 14 MacMillan D. G, Sim A. K. A comparative study of platelet aggregation in man and laboratory animals. Thrombosis et Diathesis Haemorrhagica 1970; 24: 385
    PubMedGoogle Scholar
  • 15 Mannucci P. M, Pareti F. I. Platelet functions after intravenous administration in man of cyclic AMP and related drugs. Journal of Laboratory and Clinical Medicine 1974; 84: 828
    PubMedGoogle Scholar
  • 16 Marquis N. R, Becker J. A, Vigdahl R. L. Platelet aggregation. III. An epinephrine induced decrease in cyclic AMP synthesis. Biochemical and Biophysical Research Communications 1970; 39: 783
    CrossrefPubMedGoogle Scholar
  • 17 Marquis N. R, Vigdahl R. L, Tavormina P. A. Platelet aggregation. I. Regulation by cyclic AMP and prostaglandin E1 . Biochemical and Biophysical Research Communications 1969; 36: 965
    CrossrefPubMedGoogle Scholar
  • 18 Mills D. C. B. Factors influencing the adenyl cyclase system in human blood platelets. In: S. Sherry and A. Scriabine (Eds.). Platelets and Thrombosis. University Park Press, p. 1974: 45
    Google Scholar
  • 19 Mills D. C. B, Smith J. B. The influence of platelet aggregation of drugs that affect the accumulation of adenosine 3’,5’-cyclic monophosphate in platelets. Biochemical Journal 1971; 121: 185
    CrossrefPubMedGoogle Scholar
  • 20 Mills D. C. B, Robb I. A, Roberts G. C. K. The release of nucleotides, 5-hydroxytryptamine and enzymes from human blood platelets during aggregation. Journal of Physiology 1968; 195: 715
    CrossrefPubMedGoogle Scholar
  • 21 Mills D. C. B, Roberts G. C. K. Effects of adrenaline on human blood platelets. Journal of Physiology 1967; 193: 443
    CrossrefPubMedGoogle Scholar
  • 22 Mitchell J.R. A, Sharp A. A. Platelet clumping in vitro. British Journal of Haematology 1964; 10: 78
    CrossrefPubMedGoogle Scholar
  • 23 Moskowitz J, Harwood J. P, Reid W. D, Krishna G. The interaction of norepinephrine and PGE1 on the adenyl cyclase system of human and rabbit platelets. Biochimica et Biophysica Acta 1971; 230: 279
    CrossrefPubMedGoogle Scholar
  • 24 Mustard J. F, Perry D. W, Ardlie N. G, Packham M. A. Preparation of suspensions of washed platelets from humans. British Journal of Haematology 1972; 22: 193
    CrossrefPubMedGoogle Scholar
  • 25 Mustard J. F, Packham M. A. Factors influencing platelet function: Adhesion,release, and aggregation. Pharmacological Reviews 1970; 22: 97
    PubMedGoogle Scholar
  • 26 O’Brien J. R. Some effects of adrenaline and antiadrenaline compounds on platelets in vitro and in vivo. Nature 1963; 200: 763
    CrossrefPubMedGoogle Scholar
  • 27 Robison G. A, Arnold A, Hartman R. C. Divergent effects of epinephrine and PGE1 on the level of cyclic AMP on human platelets. Pharmacological Research Communications 1969; 1: 235
    PubMedGoogle Scholar
  • 28 Sacchetti G, Bellani D, Montanari G, Gibelli A. Effects “in vitro” of some cardiovascular drugs and other agents on human platelet aggregation. Thrombosis et Diathesis Haemorrhagica 1973; 29: 190
    PubMedGoogle Scholar
  • 29 Salzman E. W. Cyclic AMP and platelet function. New England Journal of Medicine 1972; 286: 358
    CrossrefPubMedGoogle Scholar
  • 30 Salzman E. W, Neri L. L. Cyclic3’, 5’-adenosine monophosphate in human blood platelets. Nature 1969; 224: 609
    CrossrefPubMedGoogle Scholar
  • 31 Sharma H. M, Panganamala R. V, Geer J. C, Cornwell D. G. Inhibition of platelet aggregation induced by either epinephrine or arachidonic acid. Thrombosis Research 1975; 7: 879
    CrossrefPubMedGoogle Scholar
  • 32 Sinakos Z, Caen J. Platelet aggregation in mammalians (Human,rat, rabbit, Guinea-pig, horse, dog). A comparative study. Thrombosis et Diathesis Haemorrhagica 1967; 17: 99
    PubMedGoogle Scholar
  • 33 Sinakos Z, Caen J. Le comportement des plaquettes chez le rat. Thrombosis et Diathesis Haemorrhagica 1966; 16: 1963
    PubMedGoogle Scholar
  • 34 Stock K, Westermann E. Competitive and non-competitive inhibition of lipolysis by a and ß-adrenergic blocking agents, methoxamine derivatives and prostaglandin E1 . Life Sciences 1966; 5: 1667
    CrossrefPubMedGoogle Scholar
  • 35 Thomas D.P, Niewiarowski S, Ream V. Release of adenine nucleotides and platelet factor 4 from platelets of man and other species. Journal of Laboratory and Clinical Medicine 1970; 75: 608
    PubMedGoogle Scholar
  • 36 Thomas D. P. The role of platelet catecholamines in the aggregation of platelets by collagen and thrombin. In: Platelets and Hemostasis. Experimental Biology and Medicine 1968; 3: 129
    PubMedGoogle Scholar
  • 37 Zieve P. D, Greenough W. B. Adenyl cyclase in human platelets: Activity and responsiveness. Biochemical and Biophysical Research Communications 1969; 35: 462
    CrossrefPubMedGoogle Scholar