Effects of 8-(N, N-Diethylamino)Octyl 3,4,5-Trimethoxybenzoate HCI (TMB-8) on Washed Blood Platelets with Special Reference to a Specific Loss of Serotonin

E H Mürer; E Siojo

doi:10.1055/s-0038-1657126

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1982; 47(01): 59-61
DOI: 10.1055/s-0038-1657126

Original Article

Schattauer GmbH Stuttgart

Effects of 8-(N, N-Diethylamino)Octyl 3,4,5-Trimethoxybenzoate HCI (TMB-8) on Washed Blood Platelets with Special Reference to a Specific Loss of Serotonin^[*]

Authors

E H Mürer

The Thrombosis Research Center, Temple University Medical School, Philadelphia, PA, U.S.A.
E Siojo

The Thrombosis Research Center, Temple University Medical School, Philadelphia, PA, U.S.A.

Abstract

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Summary

8-(N,N-diethylamino)octyl 3,4,5-trimethoxybenzoate HCl (TMB-8) has been used to indicate involvement of Ca⁺⁺ in platelet activities, but possible other effects have not been investigated. This study investigates TMB-8-induced leakage of cytoplasmic content and specific loss of one granule constituent, serotonin from washed platelets. TMB-8 concentrations above 0.5 mM block secretion initially and induce leakage after short time incubation. TMB-8 (0.15 mM) enhances a slow release of serotonin, but inhibits a slow release of low affinity platelet factor 4 antigen which take place when washed platelets are incubated at pH 7.4 and 37°C. These effects should be taken into consideration when TMB-8 is used as a calcium antagonist in platelets.

Key words

TMB-8 - Calcium antagonists - Platelet leakage - Serotonin loss - Platelet inhibitor

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References

References
1 Rahwan RG, Piascik MF, Witiak DT. The role of calcium antagonists in the therapeutic action of drugs. Can J Physiol Pharmac 1979; 57: 443-460
2 Chiou CY, Malagodi MH. Studies on the mechanism of action of a new Ca⁺⁺ antagonist, 8-(N,N-diethylamino)octyl 3,4,5-trimethoxy-benzoate hydrochloride in smooth and skeletal muscle. Br J Pharmac 1975; 53: 279-285
3 Charo IF, Feinman RD, Detwiler TC. Inhibition of platelet secretion by an antagonist of intracellular calcium. Biochem Biophys Res Commun 1976; 72: 1462-1467
4 LeBreton GC, Dinerstein RJ. Effect of the calcium antagonist TMB-6 on intracellular calcium redistribution. Thromb Res 1977; 10: 521-523
5 LeBreton GC, Dinerstein RJ, Roth LJ, Feinberg H. Direct evidence for intracellular divalent cation re-distribution associated with platelet shape change. Biochem Biophys Res Commun 1976; 71: 362-370
6 Mürer EH, Stewart GJ, Davenport K, Siojo E, Rahwan RG, Witiak DT. Effect of three calcium antagonists on platelet secretion and metabolism. Biochem Pharmac 1981; 30: 523-530
7 Mürer EH, Davenport K, Rausch MA, Day HJ. Metabolic aspects of the secretion of stored compounds from blood platelets. V. Effect of ionophore A23187 on washed platelets. Biochim Biophys Acta 1976; 451: 1-19
8 Lages B, Scrutton MC, Holmsen H. Studies on gel filtered human platelets: Isolation and characterization in a medium containing no added Ca⁺⁺, Mg⁺⁺, K⁺ . J Lab Clin Med 1975; 85: 811-825
9 Walsh PN, Gagnatelli G. Platelet antiheparin activity: Storage site and release mechanism. Blood 1974; 44: 157-168
10 Mürer EH. Possible role of calcium in 5’-nucleotidase regulation in blood platelets. In: Calcium-Binding Proteins, Structure and Function. Siegel FL, Carafoli E, Kretsinger RH, MacLennan DH, Wasserman RH. editors 85-88 Elsevier, Amsterdam and New York: 1980
11 Holmsen H, Storm E, Day HJ. Microdetermination of ADP and ATP in the blood platelets – a modification of the plasma method. Anal Biochem 1972; 46: 489-501
12 Rucinski B, Niewiarowski S, James P, Walz DA, Budzynski AZ. Antiheparin proteins secreted by human platelets – purification, characterization and radioimmunoassay. Blood 1980; 53: 47-62
13 Robinson CP. Pharmacometrics of ω-(N,N-diethylamino)-n-alkyl-3,4,5-trimethoxybenzoates patterned after the structure of reserpine on the nervous system. Doctoral thesis, Vanderbildt University. University Microfilms, Ann Arbor, MI: 1971
14 Kaplan KL, Broekman MJ, Chernoff A, Lesznik GR, Drilling M. Platelet α-granule proteins: Studies on release and subcellular localization. Blood 1979; 53: 604-618

Effects of 8-(N, N-Diethylamino)Octyl 3,4,5-Trimethoxybenzoate HCI (TMB-8) on Washed Blood Platelets with Special Reference to a Specific Loss of Serotonin[*]

Authors

Effects of 8-(N, N-Diethylamino)Octyl 3,4,5-Trimethoxybenzoate HCI (TMB-8) on Washed Blood Platelets with Special Reference to a Specific Loss of Serotonin^[*]