Thromb Haemost 1980; 43(01): 038-040
DOI: 10.1055/s-0038-1650007
Original Article
Schattauer GmbH Stuttgart

The Interrelationship between Thromboxane Biosynthesis, Aggregation and 5-Hydroxytryptamine Secretion in Human Platelets in Vitro

L C Best
The Department of Human Metabolism and Clinical Biochemistry, University of Sheffield Medical School, Sheffield, S10 2RX, U. K.
,
T K Holland
The Department of Human Metabolism and Clinical Biochemistry, University of Sheffield Medical School, Sheffield, S10 2RX, U. K.
,
P B B Jones
The Department of Human Metabolism and Clinical Biochemistry, University of Sheffield Medical School, Sheffield, S10 2RX, U. K.
,
R G G Russell
The Department of Human Metabolism and Clinical Biochemistry, University of Sheffield Medical School, Sheffield, S10 2RX, U. K.
› Author Affiliations
Further Information

Publication History

Received 10 August 1979

Accepted 10 December 1979

Publication Date:
13 July 2018 (online)

Summary

Platelet aggregation, secretion of 5-hydroxy tryptamine and production of thromboxane B2 were monitored simultaneously in human platelet suspensions in the absence and presence of cyclooxygenase or thromboxane synthetase inhibitors. Aggregation, secretion and thromboxane B2 formation in response to either sodium arachidonate or epinephrine were blocked by aspirin or by 1-N-butyl imidazole suggesting that thromboxane biosynthesis was an essential requirement for platelet activation by these agents. In contrast, thrombin and collagen could apparently induce aggregation and secretion via two pathways: at low doses involving thromboxane production, but at higher doses by a direct mechanism independent of thromboxane biosynthesis. In the case of ADP, inhibition of thromboxane production blocked secretion but had little effect on aggregation, indicating that secretion was probably dependent on thromboxane biosynthesis which probably occurred as a result of aggregation. Thus it appears that although the processes of thromboxane production, release of dense granule constituents and aggregation may often be intimately linked, each process can occur independently of the other, depending upon the stimulus used.

 
  • References

  • 1 Smith JB, Ingerman C, Koscis JJ, Silver MJ. . J Clin Invest 1973; 52: 965-969
  • 2 Willis AL, Vane FM, Kuhn DC, Scott CG, Petrin M. . Prostaglandins 1974; 8: 453-507
  • 3 Hamberg M, Samuelsson B. . Proc Natl Acad Sci U.S.A. 1974; 71: 3400-3404
  • 4 Hamberg M, Svensson B, Samuelsson B. . Proc Natl Acad Sci U.S.A. 1975; 72: 2994-2998
  • 5 Malmsten C, Hamberg M, Svensson J, Samuelsson B. . Proc Natl Acad Sci U.S.A. 1975; 72: 1446-1450
  • 6 Samuelsson B, Hamberg M, Malmsten C, Svensson J. Advances in Prostaglandin and Thromboxane Research. 1976; 2: 737-746
  • 7 Charo IF, Feinman RD, Detwiler TC, Smith JB, Ingerman CM, Silver MJ. . Nature (Lond) 1977; 261: 66-69
  • 8 Charo IF, Feinmann RD, Detwiler TC. . J Clin Invest 1977; 60: 866-873
  • 9 Salzman EW, Lindon JN, Rodvien R. . J Cyclic Nucleotide Res 1976; 2: 25-37
  • 10 Ferraris V, Smith JB, Silver MJ. . Thromb Haemost 1977; 38: 20 (abstract)
  • 11 Maclouf J, Pradel M, Pradelles P, Dray F. . Biochem Biophys Acta 1976; 431: 139-146
  • 12 McMillan RM, MacIntyre DE, Booth A, Gordon JL. . Biochem J 1978; 176: 595-598
  • 13 Smith JB, Willis AL. . Nature New Biology 1971; 231: 235-237
  • 14 Packham MA, Guccione MA, Greenberg JP, Kinlough-Rathbone RL, Mustard JF. . Blood 1977; 50: 915-926
  • 15 Holmsen H. . Thromb Haemost 1977; 38: 1030-1041