The inflammatory and tumor-promoting sesquiterpene lactone, thapsigargin, activates platelets by selective mobilization of calcium as shown by protein phosphorylations

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The inflammatory and tumor-promoting sesquiterpene lactone, thapsigargin, activates platelets by selective mobilization of calcium as shown by protein phosphorylations. / Thastrup, Ole; Linnebjerg, H; Bjerrum, P J; Knudsen, J B; Christensen, S B.

In: BBA General Subjects, Vol. 927, No. 1, 1987, p. 65-73.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Thastrup, O, Linnebjerg, H, Bjerrum, PJ, Knudsen, JB & Christensen, SB 1987, 'The inflammatory and tumor-promoting sesquiterpene lactone, thapsigargin, activates platelets by selective mobilization of calcium as shown by protein phosphorylations', BBA General Subjects, vol. 927, no. 1, pp. 65-73.

APA

Thastrup, O., Linnebjerg, H., Bjerrum, P. J., Knudsen, J. B., & Christensen, S. B. (1987). The inflammatory and tumor-promoting sesquiterpene lactone, thapsigargin, activates platelets by selective mobilization of calcium as shown by protein phosphorylations. BBA General Subjects, 927(1), 65-73.

Vancouver

Thastrup O, Linnebjerg H, Bjerrum PJ, Knudsen JB, Christensen SB. The inflammatory and tumor-promoting sesquiterpene lactone, thapsigargin, activates platelets by selective mobilization of calcium as shown by protein phosphorylations. BBA General Subjects. 1987;927(1):65-73.

Author

Thastrup, Ole ; Linnebjerg, H ; Bjerrum, P J ; Knudsen, J B ; Christensen, S B. / The inflammatory and tumor-promoting sesquiterpene lactone, thapsigargin, activates platelets by selective mobilization of calcium as shown by protein phosphorylations. In: BBA General Subjects. 1987 ; Vol. 927, No. 1. pp. 65-73.

Bibtex

@article{39e9919e9df84215895b0e1501077e24,
title = "The inflammatory and tumor-promoting sesquiterpene lactone, thapsigargin, activates platelets by selective mobilization of calcium as shown by protein phosphorylations",
abstract = "We have studied the activation of human blood platelets by the inflammatory and tumor-promoting sesquiterpene lactone, thapsigargin. The effect of thapsigargin was compared with other common agonists (calcium ionophore A23187, phorbol ester TPA and thrombin). Platelet aggregation, serotonin release, raised cytoplasmic free calcium level and phosphorylation of platelet proteins was examined in platelet-rich plasma and washed platelet suspension. In contrast to A23187 and thrombin, the platelet activation induced by thapsigargin developed slowly, with maximal response obtained after 2-3 min. Both the thapsigargin- and the A23187-induced serotonin releases were synergistically increased by TPA. Studies of the phosphorylation of platelet proteins revealed that thapsigargin and A23187 equally well induced a selective phosphorylation of two proteins with apparent molecular masses of 20 kDa and 47 kDa. These proteins, which are substrates of myosin light-chain kinase and protein kinase C respectively, are known to be involved in platelet activation. The thapsigargin-induced platelet aggregation and serotonin release was completely inhibited by class I (nimodipine), class II (verapamil) and class III (diltiazem) calcium-channel blockers. The inhibitory activity of nimodipine was abolished by the corresponding 1,4-dihydropyridine calcium-channel agonist, BAY K 8644. These results shows that the thapsigargin-induced platelet activation is mediated by an increase in the cytoplasmic free calcium level, presumably obtained by stimulation of the passive calcium transport through specific channels. These thapsigargin-sensitive channels should predominantly be located in the membranes of intracellular calcium stores rather than in the plasma membrane, because removal of extracellular calcium by EGTA had only an insignificant effect on the thapsigargin-induced rise in cytoplasmic free calcium level.",
keywords = "Blood Platelets, Calcimycin, Calcium, Cytoplasm, Diltiazem, Humans, Kinetics, Molecular Weight, Nimodipine, Phosphoproteins, Plant Extracts, Platelet Aggregation, Serotonin, Tetradecanoylphorbol Acetate, Thapsigargin, Thrombin, Verapamil",
author = "Ole Thastrup and H Linnebjerg and Bjerrum, {P J} and Knudsen, {J B} and Christensen, {S B}",
year = "1987",
language = "English",
volume = "927",
pages = "65--73",
journal = "B B A - General Subjects",
issn = "0304-4165",
publisher = "Elsevier",
number = "1",

}

RIS

TY - JOUR

T1 - The inflammatory and tumor-promoting sesquiterpene lactone, thapsigargin, activates platelets by selective mobilization of calcium as shown by protein phosphorylations

AU - Thastrup, Ole

AU - Linnebjerg, H

AU - Bjerrum, P J

AU - Knudsen, J B

AU - Christensen, S B

PY - 1987

Y1 - 1987

N2 - We have studied the activation of human blood platelets by the inflammatory and tumor-promoting sesquiterpene lactone, thapsigargin. The effect of thapsigargin was compared with other common agonists (calcium ionophore A23187, phorbol ester TPA and thrombin). Platelet aggregation, serotonin release, raised cytoplasmic free calcium level and phosphorylation of platelet proteins was examined in platelet-rich plasma and washed platelet suspension. In contrast to A23187 and thrombin, the platelet activation induced by thapsigargin developed slowly, with maximal response obtained after 2-3 min. Both the thapsigargin- and the A23187-induced serotonin releases were synergistically increased by TPA. Studies of the phosphorylation of platelet proteins revealed that thapsigargin and A23187 equally well induced a selective phosphorylation of two proteins with apparent molecular masses of 20 kDa and 47 kDa. These proteins, which are substrates of myosin light-chain kinase and protein kinase C respectively, are known to be involved in platelet activation. The thapsigargin-induced platelet aggregation and serotonin release was completely inhibited by class I (nimodipine), class II (verapamil) and class III (diltiazem) calcium-channel blockers. The inhibitory activity of nimodipine was abolished by the corresponding 1,4-dihydropyridine calcium-channel agonist, BAY K 8644. These results shows that the thapsigargin-induced platelet activation is mediated by an increase in the cytoplasmic free calcium level, presumably obtained by stimulation of the passive calcium transport through specific channels. These thapsigargin-sensitive channels should predominantly be located in the membranes of intracellular calcium stores rather than in the plasma membrane, because removal of extracellular calcium by EGTA had only an insignificant effect on the thapsigargin-induced rise in cytoplasmic free calcium level.

AB - We have studied the activation of human blood platelets by the inflammatory and tumor-promoting sesquiterpene lactone, thapsigargin. The effect of thapsigargin was compared with other common agonists (calcium ionophore A23187, phorbol ester TPA and thrombin). Platelet aggregation, serotonin release, raised cytoplasmic free calcium level and phosphorylation of platelet proteins was examined in platelet-rich plasma and washed platelet suspension. In contrast to A23187 and thrombin, the platelet activation induced by thapsigargin developed slowly, with maximal response obtained after 2-3 min. Both the thapsigargin- and the A23187-induced serotonin releases were synergistically increased by TPA. Studies of the phosphorylation of platelet proteins revealed that thapsigargin and A23187 equally well induced a selective phosphorylation of two proteins with apparent molecular masses of 20 kDa and 47 kDa. These proteins, which are substrates of myosin light-chain kinase and protein kinase C respectively, are known to be involved in platelet activation. The thapsigargin-induced platelet aggregation and serotonin release was completely inhibited by class I (nimodipine), class II (verapamil) and class III (diltiazem) calcium-channel blockers. The inhibitory activity of nimodipine was abolished by the corresponding 1,4-dihydropyridine calcium-channel agonist, BAY K 8644. These results shows that the thapsigargin-induced platelet activation is mediated by an increase in the cytoplasmic free calcium level, presumably obtained by stimulation of the passive calcium transport through specific channels. These thapsigargin-sensitive channels should predominantly be located in the membranes of intracellular calcium stores rather than in the plasma membrane, because removal of extracellular calcium by EGTA had only an insignificant effect on the thapsigargin-induced rise in cytoplasmic free calcium level.

KW - Blood Platelets

KW - Calcimycin

KW - Calcium

KW - Cytoplasm

KW - Diltiazem

KW - Humans

KW - Kinetics

KW - Molecular Weight

KW - Nimodipine

KW - Phosphoproteins

KW - Plant Extracts

KW - Platelet Aggregation

KW - Serotonin

KW - Tetradecanoylphorbol Acetate

KW - Thapsigargin

KW - Thrombin

KW - Verapamil

M3 - Journal article

C2 - 3098302

VL - 927

SP - 65

EP - 73

JO - B B A - General Subjects

JF - B B A - General Subjects

SN - 0304-4165

IS - 1

ER -

ID: 43350572