Abstract
A23187 is an antibiotic ionophore which transports divalent cations across cell membranes into the cytoplasm and releases cations from intracellular storage sites. The present investigation has studied the influence of A23187 on blood platelet aggregation and secretion. A23187 added to stirred C-PRP produced concentration-dependent aggregation and release of 14C-serotonin. Calcium ions potentiated the response of platelets in washed suspensions to A23187, but they were not required for ionophore-induced aggregation or release. N-ethylmaleimide and agents which increase the level of cyclic 3′,5′-adenosine monophosphate (cAMP) in platelets were effective inhibitors of A23187-induced aggregation and secretion.Platelets incubated with 45Ca++ before addition of A23187 increased their content of isotope by 50% within 45 seconds after exposure to the ionophore. The results indicate that an increase in the cytoplasmic concentration of calcium ions from intracellular sources may be the critical event in triggering platelet contraction and the release reaction. Increased concentrations of cAMP may inhibit the platelet response to A23187 and other aggregating agents by stimulating a calcium extrusion pump.
Full text
PDF















Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Behnke O. The morphology of blood platelet membrane systems. Ser Haematol. 1970;3(4):3–16. [PubMed] [Google Scholar]
- Bettex-Galland M., Lüscher E. F. Thrombosthenin, the contractile protein from blood platelets and its relation to other contractile proteins. Adv Protein Chem. 1965;20:1–35. doi: 10.1016/s0065-3233(08)60387-3. [DOI] [PubMed] [Google Scholar]
- Born G. V. Current ideas on the mechanism of platelet aggregation. Ann N Y Acad Sci. 1972 Oct 27;201:4–12. doi: 10.1111/j.1749-6632.1972.tb16283.x. [DOI] [PubMed] [Google Scholar]
- Bygdeman S., Stjärne L. Calcium uptake and collagen-induced platelet release reaction. Scand J Haematol. 1971;8(3):183–188. doi: 10.1111/j.1600-0609.1971.tb01971.x. [DOI] [PubMed] [Google Scholar]
- Chambers D. A., Salzman E. W., Neri L. L. Characterization of "ecto-ATPase" of human blood platelets. Arch Biochem Biophys. 1967 Mar;119(1):173–178. doi: 10.1016/0003-9861(67)90444-4. [DOI] [PubMed] [Google Scholar]
- Clawson C. C., White J. G. Platelet interaction with bacteria. I. Reaction phases and effects of inhibitors. Am J Pathol. 1971 Nov;65(2):367–380. [PMC free article] [PubMed] [Google Scholar]
- Cohen I., Cohen C. A tropomyosin-like protein from human platelets. J Mol Biol. 1972 Jul 21;68(2):383–387. doi: 10.1016/0022-2836(72)90220-3. [DOI] [PubMed] [Google Scholar]
- Day H. J., Holmsen H. Concepts of the blood platelet release reaction. Ser Haematol. 1971;4(1):3–27. [PubMed] [Google Scholar]
- Dietze G., Hepp K. D. Effect of 3'5'-AMP on calcium-activated ATPase in rat heart sarcolemma. Biochem Biophys Res Commun. 1972 Jan 14;46(1):269–278. doi: 10.1016/0006-291x(72)90659-6. [DOI] [PubMed] [Google Scholar]
- Foreman J. C., Mongar J. L., Gomperts B. D. Calcium ionophores and movement of calcium ions following the physiological stimulus to a secretory process. Nature. 1973 Oct 5;245(5423):249–251. doi: 10.1038/245249a0. [DOI] [PubMed] [Google Scholar]
- GRETTE K. Relaxing factor in extracts of blood platelets and its function in the cells. Nature. 1963 May 4;198:488–489. doi: 10.1038/198488a0. [DOI] [PubMed] [Google Scholar]
- GRETTE K. Studies on the mechanism of thrombin-catalyzed hemostatic reactions in blood platelets. Acta Physiol Scand Suppl. 1962;195:1–93. [PubMed] [Google Scholar]
- Gerrard J. M., White J. G., Rao G. H. Effects of the lonophore A23187 on the blood platelets II. Influence on ultrastructure. Am J Pathol. 1974 Nov;77(2):151–166. [PMC free article] [PubMed] [Google Scholar]
- Jerushalmy Z., Zucker M. B. Some effects of fibrinogen degradation products (FDP) on blood platelets. Thromb Diath Haemorrh. 1966 May 15;15(3):413–419. [PubMed] [Google Scholar]
- Leathwood P. D., Gilford M. K., Plummer D. T. Enzymes in rat urine: lactate dehydrogenase. Enzymologia. 1972 Apr 28;42(4):285–301. [PubMed] [Google Scholar]
- Lüscher E. F., Probst E., Bettex-Galland M. Thrombosthenin: structure and function. Ann N Y Acad Sci. 1972 Oct 27;201:122–130. doi: 10.1111/j.1749-6632.1972.tb16293.x. [DOI] [PubMed] [Google Scholar]
- Martin J. H., Carson F. L., Race G. J. Calcium-containing platelet granules. J Cell Biol. 1974 Mar;60(3):775–777. doi: 10.1083/jcb.60.3.775. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mürer E. H., Holme R. A study of the release of calcium from human blood platelets and its inhibition by metabolic inhibitors. N-ethylmaleimide and aspirin. Biochim Biophys Acta. 1970 Oct 27;222(1):197–205. doi: 10.1016/0304-4165(70)90365-x. [DOI] [PubMed] [Google Scholar]
- Pressman B. C. Properties of ionophores with broad range cation selectivity. Fed Proc. 1973 Jun;32(6):1698–1703. [PubMed] [Google Scholar]
- Prince W. T., Rasmussen H., Berridge M. J. The role of calcium in fly salivary gland secretion analyzed with the ionophore A-23187. Biochim Biophys Acta. 1973 Nov 2;329(1):98–107. doi: 10.1016/0304-4165(73)90012-3. [DOI] [PubMed] [Google Scholar]
- Rasmussen H. Cell communication, calcium ion, and cyclic adenosine monophosphate. Science. 1970 Oct 23;170(3956):404–412. doi: 10.1126/science.170.3956.404. [DOI] [PubMed] [Google Scholar]
- Reed P. W., Lardy H. A. A23187: a divalent cation ionophore. J Biol Chem. 1972 Nov 10;247(21):6970–6977. [PubMed] [Google Scholar]
- Robblee L. S., Shepro D., Belamarich F. A. Calcium uptake and associated adenosine triphosphatase activity of isolated platelet membranes. J Gen Physiol. 1973 Apr;61(4):462–481. doi: 10.1085/jgp.61.4.462. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Robblee L. S., Shepro D., Belamarich F. A., Towle C. Platelet calcium flux and the release reaction. Ser Haematol. 1973;6(3):311–316. [PubMed] [Google Scholar]
- Salzman E. W. Cyclic AMP and platelet function. N Engl J Med. 1972 Feb 17;286(7):358–363. doi: 10.1056/NEJM197202172860708. [DOI] [PubMed] [Google Scholar]
- Salzman E. W., Kensler P. C., Levine L. Cyclic 3',5'-adenosine monophosphate in human blood platelets. IV. Regulatory role of cyclic amp in platelet function. Ann N Y Acad Sci. 1972 Oct 27;201:61–71. doi: 10.1111/j.1749-6632.1972.tb16287.x. [DOI] [PubMed] [Google Scholar]
- Scarpa A., Baldassare J., Inesi G. The effect of calcium ionophores on fragmented sarcoplasmic reticulum. J Gen Physiol. 1972 Dec;60(6):735–749. doi: 10.1085/jgp.60.6.735. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Smith J. B., Ingerman C., Kocsis J. J., Silver M. J. Formation of prostaglandins during the aggregation of human blood platelets. J Clin Invest. 1973 Apr;52(4):965–969. doi: 10.1172/JCI107262. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Statland B. E., Heagan B. M., White J. G. Uptake of calcium by platelet relaxing factor. Nature. 1969 Aug 2;223(5205):521–522. doi: 10.1038/223521a0. [DOI] [PubMed] [Google Scholar]
- Walsh P. N. Albumin density gradient separation and washing of platelets and the study of platelet coagulant activities. Br J Haematol. 1972 Feb;22(2):205–217. doi: 10.1111/j.1365-2141.1972.tb08801.x. [DOI] [PubMed] [Google Scholar]
- Weiss H. J., Ames R. P. Ultrastructural findings in storage pool disease and aspirin-like defects of platelets. Am J Pathol. 1973 Jun;71(3):447–466. [PMC free article] [PubMed] [Google Scholar]
- White J. G., Edson J. R., Desnick S. J., Witkop C. J., Jr Studies of platelets in a variant of the Hermansky-Pudlak syndrome. Am J Pathol. 1971 May;63(2):319–332. [PMC free article] [PubMed] [Google Scholar]
- White J. G. Electron microscopic studies of platelet secretion. Prog Hemost Thromb. 1974;2(0):49–98. [PubMed] [Google Scholar]
- White J. G. Fine structural alterations induced in platelets by adenosine diphosphate. Blood. 1968 May;31(5):604–622. [PubMed] [Google Scholar]
- White J. G. Interaction of membrane systems in blood platelets. Am J Pathol. 1972 Feb;66(2):295–312. [PMC free article] [PubMed] [Google Scholar]
- White J. G., Krivit W. Fine structural localization of adenosine triphosphatase in human platelets and other blood cells. Blood. 1965 Nov;26(5):554–568. [PubMed] [Google Scholar]
- White J. G., Rao G. H., Estensen R. D. Investigation of the release reaction in platelets exposed to phorbol myristate acetate. Am J Pathol. 1974 May;75(2):301–314. [PMC free article] [PubMed] [Google Scholar]
- White J. G. The interplatelet zone. Am J Pathol. 1970 Jan;58(1):19–29. [PMC free article] [PubMed] [Google Scholar]
- White J. G. Uptake of latex particles by blood platelets: phagocytosis or sequestration? Am J Pathol. 1972 Dec;69(3):439–458. [PMC free article] [PubMed] [Google Scholar]
- Wong D. T., Wilkinson J. R., Hamill R. L., Horng J. S. Effects of antibiotic ionophore, A23187, on oxidative phosphorylation and calcium transport of liver mitochondria. Arch Biochem Biophys. 1973 Jun;156(2):578–585. doi: 10.1016/0003-9861(73)90308-1. [DOI] [PubMed] [Google Scholar]