Competitive Inhibition by Lithium and Hydrogen lons of the Effect of Calcium on the Aggregation of Rabbit Platelets

Esther R. Anderson; J. G Foulks

doi:10.1055/s-0038-1648050

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1976; 36(02): 343-359
DOI: 10.1055/s-0038-1648050

Original Article

Schattauer GmbH

Competitive Inhibition by Lithium and Hydrogen lons of the Effect of Calcium on the Aggregation of Rabbit Platelets

Esther R. Anderson

¹Department of Pharmacology, Faculty of Medicine, The University of British Columbia, Vancouver, B. C., V6T 1W5 Canada

,

J. G Foulks

¹Department of Pharmacology, Faculty of Medicine, The University of British Columbia, Vancouver, B. C., V6T 1W5 Canada

› Author Affiliations

Abstract

Summary

ADP-induced platelet aggregation and shape change were monitored optically in citrated rabbit platelet-rich plasma (PRP) diluted with isotonic salt solutions. Lithium (Li) produced a concentration-dependent reduction in the rate of platelet aggregation but had no discernible effect on the shape change which precedes aggregation. When PRP was pre-incubated with Li, the inhibitory effect of the ion was independent of the duration and temperature of the treatment. The inhibitory effect of Li also was observed in heparinized PRP or when 5-HT was used as the aggregation-inducing agent. When Li was combined with aggregation inhibitors which enhance platelet cyclic AMP content either by activating adenylate cyclase or by inhibiting phosphodiesterase, only additive effects were observed. The inhibitory effect of Li was opposed by added calcium. Kinetic evaluation of the interaction between Li and Ca indicated that their antagonism was competitive. Added calcium also displayed competitive antagonism toward the aggregation inhibiting effect of increased hydrogen ion concentration in the pH range between 6 and 8.

Full Text

References

References
1 Birch N. J. 1973; The role of magnesium and calcium in the pharmacology of lithium. Biological Psychology 7: 269.
2 Birch N.L, Hullin R. P, Inie R. A, Leaf F. C. 1974; Effects of lithium on the activity of pyruvate kinase and other magnesium dependent enzymes. British Journal of Pharmacology 52: 139
3 Birch N. J, Jenner F. A. 1973; The distribution of lithium and its effects on the distribution of other ions in the rat. British Journal of Pharmacology 47: 586.
4 Born G. V. R. 1970a Observations on the change in shape of blood platelets brought about by adenosine diphosphate. Journal of Physiology 209: 487.
5 Born G. V. R. 1970b Drugs interfering with platelet function. In: Jones R. J. (ed.) Atherosclerosis. Proceedings of the Second International Symposium. Chicago, 2–5 November 1969 Springer-Verlag; Berlin: 521.
6 Born G. V. R, Cross M. J. 1964; Effects of inorganic ions and of plasma proteins on the aggregation of blood platelets by adenosine diphosphate. Journal of Physiology 170: 397.
7 Bruno J. J, Taylor L. A, Droller M. J. 1974; Effects of prostaglandin E₂ on human platelet adenyl cyclase and aggregation. Nature 251: 721.
8 de Meis L. 1969; Ca²⁺ uptake and acetyl phosphatase of skeletal muscle. Journal of Biological Chemistry 244: 3733.
9 Dixon M. 1953; The determination of enzyme inhibitor constants. Biochemical Journal 55: 170.
10 Dousa T, Hechter O. 1970a Lithium and brain adenyl cyclase. Lancet 1: 834.
11 Dousa T, Hechter O. 1970b The effect of NaCl and LiCl on vasopressin-sensitive adenyl cyclase. Life Sciences 9: 765.
12 Drummond A. H, Gordon J. L. 1974; Platelet release reaction induced by 5-hydroxytryptamine. Journal of Physiology 240: 39
13 Fantin G. P, Bottechia D. 1974; Effect of manganese on the ADP-induced platelet aggregation. Experentia 30: 555.
14 Flatow F. A, Freireich E. J. 1966; The increased effectiveness of platelet concentrates prepared in acidified plasma. Blood 27: 449.
15 Forbes C. D, McNicol G. P, Douglas A. S. 1969; Action of a pyrimido-pyrimidine compound on platelet behaviour in vitro . British Medical Journal 2: 483.
16 Geerdink P, Levy-Toledano S, Wessels H, Caen J, Haanen C. 1972; Influence of lithium on aggregation, release-reaction and function of human platelets. Pathologie-Biologie 20 Suppl. 15.
17 Gordon J. L, MacIntyre D. E. 1975 Effects of prostaglandins E₁, E₂ and D₂ on platelet aggregation: Variation with animal species and ionized calcium concentration. In: Proceedings of the British Pharmacological Society,. 15–17 September. Abstract C. 22.
18 Greil W, Sold M, Patscheke H, Brossmer L. 1973. Effect of Li⁺, Na⁺ and K⁺ on Ca⁺⁺ dependent human platelet aggregation: Stimulation by K⁺, inhibition by Li⁺ . In: Gerlach E, Moser K, Deutsch E, Wilmanns W. (eds.), Erythrocytes, Thrombocytes, Leukocytes. Recent Advances in Membrane and Metabolic Research. IInd International Symposium; Vienna: June, 1972 284-286.
19 Han P, Ardlee N. G. 1974; The influence of pH, temperature, and calcium on platelet aggregation: Maintenance of environmental pH and platelet function of in vitro studies in plasma stored at 37° C. British Journal of Haematology 26: 373.
20 Hussanein A. A, Turpie A. G. G, McNicol G. P, Douglas A. S. 1970; Effect of RA233 on platelet function in vitro . British Medical Journal 2: 83.
21 Kinlough-Rathbone R. L, Chahil A, Mustard J. F. 1974; Divalent cations and the release reaction of pig platelets. American Journal of Physiology 226: 235.
22 Kinlough-Rathbone R. L, Packham M. A, Mustard J. F. 1970; The effect of glucose on adenosine diphosphate-induced platelet aggregation. Journal of Laboratory and Clinical Medicine 75: 780.
23 Kloeze J. 1967. Influence of prostaglandins on platelet adhesiveness and platelet aggregation. In: Berstrom S, Samuelsson B. (eds.), Prostaglandins. Interscience, publishers; New York: 241.
24 Lamberth JR, Warriner E. L, III R. A, Batchelor E. D. 1974; Effect of metabolic acidosis and alkalosis on human platelet aggregation induced by epinephrine and ADP. In: Proceedings of the Society for Experimental Biology and Medicine 145: 743.
25 Lineweaver H, Burk D. 1934; The determination of enzyme dissociation constants. Journal of the American Chemical Society 56: 658.
26 McLean J. R, Veloso H. 1967; Change in shape without aggregation caused by ADP in rabbit platelets at low pH. Life Sciences 6: 1983.
27 Marquis N. R, Vigdahl R. L, Tavormina P. A. 1969; Platelet aggregation. I. Regulation by cyclic AMP and prostaglandin E₁ . Biochemical and Biophysical Research Communications 36: 965.
28 Michal F, Born G. V. R. 1971; Effects of the rapid shape change of platelets on the transmission and scattering of light through plasma. Nature New Biology 231: 220.
29 Mills D. C. B, Smith J. B. 1971; The influence on platelet aggregation of drugs that affect the accumulation of adenosine 3’,5’-cyclic monophosphate in platelets. Biochemical Journal 121: 185.
30 Mürer E. H. 1972; Factors influencing the initiation and extrusion phase of the platelet release reaction. Biochimica et Biophysica Acta 261: 435.
31 Murphy D. L, Donnelly C, Moskowitz J. 1973; Inhibition by lithium of prostaglandin E₁ and norepinephrine effects on cyclic adenosine monophosphate production in human platelets. Clinical Pharmacology and Therapeutics 14: 810.
32 Ohnishi T, Ebashi S. 1963; Spectrophotometrical measurement of instantaneous calcium binding of the relaxing factor of muscle. Journal of Biochemistry 54: 506.
33 Packham M. A, Guccione M. A, Chang P.-L, Mustard J. F. 1973; Platelet aggregation and release: Effects of low concentrations of thrombin or collagen. American Journal of Physiology 225: 38.
34 Pedersen K. O. 1972; Binding of calcium to serum albumin. II. Effect of pH via competitive hydrogen and calcium binding to imidazole groups of albumin. Scandinavian Journal of Clinical and Laboratory Investigation 29: 75.
35 Robblee L. S, Shepro D, Kiss J, Belamarich F. A. 1975; The effect of lanthanum on calcium flux in calf platelets. In: Federation Proceedings 13-18 April 1975 34 (03) Abstract No. 764 355.
36 Rogers A. B. 1972; The effect of pH on human platelet aggregation induced by epinephrine and ADP. In: Proceedings of the Society for Experimental Biology and Medicine 139: 1100.
37 Rozenberg M. C, Holmsen H. 1968; Adenine nucleotide metabolism of blood platelets. II. Uptake of adenosine and inhibition of ADP-induced platelet aggregation. Biochimica et biophysica Acta 155: 342.
38 Salzman E. W. 1972; Cyclic AMP and platelet function. New England Journal of Medicine 286: 358.
39 Salzman E. W, Levine L. 1971; Cyclic 3’,5’-adenosine monophosphate in human blood platelets. II. Effect of N⁶-2’-0-dibutyryl cyclic 3’,5’-adenosine monophosphate on platelet function. Journal of Clinical Investigation 50: 131.
40 Scarpa A. 1972. Spectrophotometric measurement of Ca by murexide. In: San Pietro A. (ed.), Methods in Enzymology, vol. 24. Academic Press; New York: 343.
41 Skoza L, Zucker M. B, Jerushalmy Z, Grant R. 1967; Kinetic studies of platelet aggregation induced by adenosine diphosphate and its inhibition by chelating agents, guanidino compounds and adenosine. Thrombosis et Diathesis Haemorrhagica 18: 713.
42 Vigdahl R. L, Marquis N. R, Tavormina P. A. 1969; Platelet aggregation. II. Adenyl cyclase, prostaglandin E₁ and calcium. Biochemical and Biophysical Research Communications 37: 409.
43 Wang Y.-C, Pandey G. N, Mendels J, Frazer A. 1974; Effect of lithium on prostaglandin E₁-stimulated adenylate cyclase activity of human platelets. Biochemical Pharmacology 23: 845.
44 Waud D. R. 1968; Pharmacological receptors. Pharmacology Review 20: 49.
45 Zieve P. D, Greenough W. B. 1969; Adenylcyclase in human platelets: activity and responsiveness. Biochemical and Biophysical Research Communications 35: 462.
46 Zucker M. B. 1975; Effect of heparin on platelet function. Thrombosis et Diathesis Haemorrhagica 33: 63.