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

Shuichi Hashimoto; Sachiko Shibata; Bonro Kobayashi

doi:10.1055/s-0038-1646667

Thrombosis and Haemostasis, Inhaltsverzeichnis

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

› Institutsangaben

Abstract

als PDF herunterladen

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.

PDF (831 kb)

Referenzen

References
1 Abdulla YH. 1969; β-Adrenergic receptors in human platelets. Journal of Atherosclerosis Research 9: 171
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
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
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
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
6 Hashimoto S, Shibata S, Kobayashi B. 1975; Dependence of platelet adenyl cyclase system on oxidative phosphorylation. Thrombosis et Diathesis Haemorrhagica 34: 42
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
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
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
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
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
12 Laraia PJ, Reddy WJ. 1969; Hormonal regulation of myocardial adenosine 3′, 5′-monophosphate. Biochimica et Biophysica Acta 177: 189
13 Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. 1951; Protein measurment with the Folin phenol reagent. Journal of Biological Chemistry 193: 265
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
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
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
17 Shibata S, Kobayashi B. 1975; Light scattering changes of edetic acid-treated, washed rat platelets. Thrombosis et Diathesis Haemorrhagica 33: 508
18 Vigdahl RL, Marquis NR, Tavormina PA. 1969; Platelet aggregation. II. Adenyl cyclase prostaglandin E₁, calcium. Biochemical Biophysical Research Communications 37: 409
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
20 Wolfe SM, Shulman NR. 1969; Adenyl cyclase activity in human platelets. Biochemical and Biophysical Research Communications 35: 265
21 Zieve PD, Greenough WB. 1969; Adenyl cyclase in human platelets. activity responsiveness. Biochemical and Biophysical Research Communications 35: 462