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Thromb Haemost 1978; 39(01): 177-185
DOI: 10.1055/s-0038-1646667
Original Article
Schattauer GmbH Stuttgart

The Effect of Mitomycin C on Platelet Aggregation and Adenosine 3′, 5′-Monophosphate Metabolism

Shuichi Hashimoto
The Radioisotope Research Laboratory and Department of Physiological Chemistry, School of Pharmaceutical Sciences, Kitasato University, Tokyo 108, Japan
,
Sachiko Shibata
The Radioisotope Research Laboratory and Department of Physiological Chemistry, School of Pharmaceutical Sciences, Kitasato University, Tokyo 108, Japan
,
Bonro Kobayashi
The Radioisotope Research Laboratory and Department of Physiological Chemistry, School of Pharmaceutical Sciences, Kitasato University, Tokyo 108, Japan
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Publication History

Received 06 March 1977

Accepted 15 July 1977

Publication Date:
12 July 2018 (online)

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Summary

The effect of Mitomycin C on aggregation, adenosine 3′, 5′-monophosphate (cyclic AMP) metabolism and reactions induced by thrombin was studied in rabbit platelets. Mitomycin C inhibited the platelet aggregation induced by adenosine diphosphate or thrombin. The level of radioactive cyclic AMP derived from 8-14C adenine or 8-14C adenosine increased after incubating intact platelets with Mitomycin G. Formation of radioactive adenosine triphosphate also increased though mitochondrial oxidation was not stimulated. Similar effect was observed also in rabbit liver. Mitomycin C failed to stimulate platelet adenyl cyclase but inhibited cyclic AMP phosphodiesterase in the absence of theophylline. In the platelets preincubated with Mitomycin C, thrombin-induced inhibition of adenyl cyclase, stimulation of membrane-bound cyclic AMP phosphodiesterase, and release of 250,000 dalton protein from platelet membranes were prevented. These results suggest that Mitomycin C will affect cellular membrane structure and function, and this extranuclear effect of Mitomycin C will lead to inhibition of aggregation in blood platelets.

 

  • References

  • 1 Abdulla YH. 1969; β-Adrenergic receptors in human platelets. Journal of Atherosclerosis Research 9: 171
    CrossrefPubMedGoogle Scholar
  • 2 Ardlie NG, Glew G, Schultz BG, Schwartz CJ. 1967; Inhibition and reversal of platelet aggregation by methyl xanthines. Thrombosis et Diathesis Haemorrhagica 18: 670
    PubMedGoogle Scholar
  • 3 Ardlie NG, Packham MA, Mustard JF. 1970; Adenosine diphosphate-induced platelet aggregation in suspensions of washed rabbit platelets. British Journal of Haematology 19: 7
    CrossrefPubMedGoogle Scholar
  • 4 Ball G, Brereton GG, Fulwood M, Ireland DM, Yates P. 1970; Effect of prostaglandin E1 alone and in combination with theophylline or aspirin on collagen-induced platelet aggregation and on platelet nucleotides including adenosine 3′, 5′-cyclic monophosphate. Biochemical Journal 120: 709
    CrossrefPubMedGoogle Scholar
  • 5 Boullin DJ, Green AR, Price KS. 1972; The mechanism of adenosine diphosphate-induced platelet aggregation. binding to platelet receptors and inhibition of binding and aggregation by prostaglandin E1 . Journal of Physiology (London) 221: 415
    CrossrefPubMedGoogle Scholar
  • 6 Hashimoto S, Shibata S, Kobayashi B. 1975; Dependence of platelet adenyl cyclase system on oxidative phosphorylation. Thrombosis et Diathesis Haemorrhagica 34: 42
    PubMedGoogle Scholar
  • 7 Hashimoto S, Shibata S, Kobayashi B. 1977; Exterior and interior events in early stage of thrombin-induced platelet aggregation. Thrombosis and Haemastasis 38: 630
    PubMedGoogle Scholar
  • 8 Haslam RJ. 1975. Roles of cyclic nucleotides in platelet function. In: Biochemistry and Pharmacology of Platelets. Ciba Foundation Symposium 35 (new series). Elsevier Excerpta Medica; North-Holland: 121
    Google Scholar
  • 9 Hata T, Sano Y, Sugawara R, Matsumae A, Kanamori K, Shima T, Hoshi T. 1956; Mitomycin, a new antibiotic from streptomyces. I. Journal of Antibiotics (Japan) ser A: 9-141
    PubMedGoogle Scholar
  • 10 Iyer VN, Szybalski W. 1963; A molecular mechanism of mitomycin action linking of complementary DNA strands. Proceedings of the National Academy of Science, USA 50: 355
    CrossrefPubMedGoogle Scholar
  • 11 Krishna G, Weiss B, Brodie BB. 1968; A simple, sensitive method for the assay of adenyl cyclase. Journal of Pharmacology and Experimental Therapeutics 163: 379
    PubMedGoogle Scholar
  • 12 Laraia PJ, Reddy WJ. 1969; Hormonal regulation of myocardial adenosine 3′, 5′-monophosphate. Biochimica et Biophysica Acta 177: 189
    CrossrefPubMedGoogle Scholar
  • 13 Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. 1951; Protein measurment with the Folin phenol reagent. Journal of Biological Chemistry 193: 265
    PubMedGoogle Scholar
  • 14 Michal F, Born GVR. 1971; Effect of the rapid shape change of platelets on the transmission and scattering of light through plasma. Nature New Biology 231: 220
    PubMedGoogle Scholar
  • 15 Salzman EW, Weisenberger H. 1972. Role of cyclic AMP in platelet function. In: Greengard P, Robison GA. (eds.) Advances in Cyclic Nucleotide Research. Volume 1. Physiology and Pharmacology of Cyclic AMP. Raven Press; New York: 231
    Google Scholar
  • 16 Sedlak J, Lindsay RH. 1968; Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman’s reagent. Analytical Biochemistry 25: 192
    CrossrefPubMedGoogle Scholar
  • 17 Shibata S, Kobayashi B. 1975; Light scattering changes of edetic acid-treated, washed rat platelets. Thrombosis et Diathesis Haemorrhagica 33: 508
    PubMedGoogle Scholar
  • 18 Vigdahl RL, Marquis NR, Tavormina PA. 1969; Platelet aggregation. II. Adenyl cyclase prostaglandin E1, calcium. Biochemical Biophysical Research Communications 37: 409
    CrossrefPubMedGoogle Scholar
  • 19 Weber E, Walter E, Morgenstern E, Mondt H, Rose U, Towliati H, Knaudt E. 1970; Untersuchungen an fraktionierten Plättchenhomogenaten-1. Zur Charakterisierung dreier lysosomaler Enzyme und über die Differenzierung des alpha-Glanulomer. Biochemical Pharmacology 19: 1893
    CrossrefPubMedGoogle Scholar
  • 20 Wolfe SM, Shulman NR. 1969; Adenyl cyclase activity in human platelets. Biochemical and Biophysical Research Communications 35: 265
    CrossrefPubMedGoogle Scholar
  • 21 Zieve PD, Greenough WB. 1969; Adenyl cyclase in human platelets. activity responsiveness. Biochemical and Biophysical Research Communications 35: 462
    CrossrefPubMedGoogle Scholar