Diacylglycerol causes Ca release from the platelet dense tubular system: comparisons with Ca release caused by inositol 1,4,5-triphosphate

Lawrence F. Brass, Michael Laposata

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Platelet activation is often associated with an increase in the cytosolic free Ca concentration that is due in part to Ca release from the dense tubular system. The present studies examine whether the diacylglycerol formed by phosphoinositide hydrolysis during platelet activation contributes to this process. The effect of diacylglycerol on the dense tubular system was tested using platelets that were permeabilized with saponin and then allowed to accumulate 45Ca. A synthetic diacylglycerol, 1-oleoyl-2-acetoyl glycerol (OAG), released up to 70% of the ionophore A23187-releasable 45Ca, a fraction identical to that discharged by inositol 1,4,5-triphosphate (IP3) under the same conditions. 45Ca release was half-maximal at 40 μM OAG and 1 μM IP3. The response to OAG was not inhibited by aspirin and could not be reproduced by the addition of a phorbol ester, which suggests that it involves neither arachidonic acid metabolism nor protein kinase C activation. The time course of OAG-induced 45Ca release, which was slower than IP3-induced 45Ca release, corresponded to the time course of conversion of the OAG to 1-oleoyl-2-acetoyl phosphatidic acid (OAG-PA). When either OAG-PA or lysophosphatidic acid was added to the saponin-treated platelets, the extent of 45Ca release was similar to that observed with OAG, but both the OAG-PA and the lysophosphatidic acid were 5 to 10 times more potent than OAG on a molar basis. These data suggest: (1) that the Ca release caused by diacylglycerol is actually due to formation of phosphatidic acid and/or lysophosphatidic acid, (2) that these molecules are not acting as simple Ca ionophores and (3) that diacylglycerol metabolites may augment the changes in Ca homeostasis caused by IP3 during platelet activation.

Original languageEnglish (US)
Pages (from-to)7-14
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume142
Issue number1
DOIs
StatePublished - Jan 15 1987
Externally publishedYes

Fingerprint

Inositol 1,4,5-Trisphosphate
Diglycerides
Platelets
Glycerol
Blood Platelets
Chemical activation
Platelet Activation
Phosphatidic Acids
Ionophores
Saponins
monoolein
Phorbol Esters
Metabolites
Phosphatidylinositols
Calcimycin
Arachidonic Acid
Metabolism
Protein Kinase C
Aspirin
Hydrolysis

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

@article{0689484ba6ab4c1b91ea1c854a2e4758,
title = "Diacylglycerol causes Ca release from the platelet dense tubular system: comparisons with Ca release caused by inositol 1,4,5-triphosphate",
abstract = "Platelet activation is often associated with an increase in the cytosolic free Ca concentration that is due in part to Ca release from the dense tubular system. The present studies examine whether the diacylglycerol formed by phosphoinositide hydrolysis during platelet activation contributes to this process. The effect of diacylglycerol on the dense tubular system was tested using platelets that were permeabilized with saponin and then allowed to accumulate 45Ca. A synthetic diacylglycerol, 1-oleoyl-2-acetoyl glycerol (OAG), released up to 70{\%} of the ionophore A23187-releasable 45Ca, a fraction identical to that discharged by inositol 1,4,5-triphosphate (IP3) under the same conditions. 45Ca release was half-maximal at 40 μM OAG and 1 μM IP3. The response to OAG was not inhibited by aspirin and could not be reproduced by the addition of a phorbol ester, which suggests that it involves neither arachidonic acid metabolism nor protein kinase C activation. The time course of OAG-induced 45Ca release, which was slower than IP3-induced 45Ca release, corresponded to the time course of conversion of the OAG to 1-oleoyl-2-acetoyl phosphatidic acid (OAG-PA). When either OAG-PA or lysophosphatidic acid was added to the saponin-treated platelets, the extent of 45Ca release was similar to that observed with OAG, but both the OAG-PA and the lysophosphatidic acid were 5 to 10 times more potent than OAG on a molar basis. These data suggest: (1) that the Ca release caused by diacylglycerol is actually due to formation of phosphatidic acid and/or lysophosphatidic acid, (2) that these molecules are not acting as simple Ca ionophores and (3) that diacylglycerol metabolites may augment the changes in Ca homeostasis caused by IP3 during platelet activation.",
author = "Brass, {Lawrence F.} and Michael Laposata",
year = "1987",
month = "1",
day = "15",
doi = "10.1016/0006-291X(87)90444-X",
language = "English (US)",
volume = "142",
pages = "7--14",
journal = "Biochemical and Biophysical Research Communications",
issn = "0006-291X",
publisher = "Academic Press Inc.",
number = "1",

}

TY - JOUR

T1 - Diacylglycerol causes Ca release from the platelet dense tubular system

T2 - comparisons with Ca release caused by inositol 1,4,5-triphosphate

AU - Brass, Lawrence F.

AU - Laposata, Michael

PY - 1987/1/15

Y1 - 1987/1/15

N2 - Platelet activation is often associated with an increase in the cytosolic free Ca concentration that is due in part to Ca release from the dense tubular system. The present studies examine whether the diacylglycerol formed by phosphoinositide hydrolysis during platelet activation contributes to this process. The effect of diacylglycerol on the dense tubular system was tested using platelets that were permeabilized with saponin and then allowed to accumulate 45Ca. A synthetic diacylglycerol, 1-oleoyl-2-acetoyl glycerol (OAG), released up to 70% of the ionophore A23187-releasable 45Ca, a fraction identical to that discharged by inositol 1,4,5-triphosphate (IP3) under the same conditions. 45Ca release was half-maximal at 40 μM OAG and 1 μM IP3. The response to OAG was not inhibited by aspirin and could not be reproduced by the addition of a phorbol ester, which suggests that it involves neither arachidonic acid metabolism nor protein kinase C activation. The time course of OAG-induced 45Ca release, which was slower than IP3-induced 45Ca release, corresponded to the time course of conversion of the OAG to 1-oleoyl-2-acetoyl phosphatidic acid (OAG-PA). When either OAG-PA or lysophosphatidic acid was added to the saponin-treated platelets, the extent of 45Ca release was similar to that observed with OAG, but both the OAG-PA and the lysophosphatidic acid were 5 to 10 times more potent than OAG on a molar basis. These data suggest: (1) that the Ca release caused by diacylglycerol is actually due to formation of phosphatidic acid and/or lysophosphatidic acid, (2) that these molecules are not acting as simple Ca ionophores and (3) that diacylglycerol metabolites may augment the changes in Ca homeostasis caused by IP3 during platelet activation.

AB - Platelet activation is often associated with an increase in the cytosolic free Ca concentration that is due in part to Ca release from the dense tubular system. The present studies examine whether the diacylglycerol formed by phosphoinositide hydrolysis during platelet activation contributes to this process. The effect of diacylglycerol on the dense tubular system was tested using platelets that were permeabilized with saponin and then allowed to accumulate 45Ca. A synthetic diacylglycerol, 1-oleoyl-2-acetoyl glycerol (OAG), released up to 70% of the ionophore A23187-releasable 45Ca, a fraction identical to that discharged by inositol 1,4,5-triphosphate (IP3) under the same conditions. 45Ca release was half-maximal at 40 μM OAG and 1 μM IP3. The response to OAG was not inhibited by aspirin and could not be reproduced by the addition of a phorbol ester, which suggests that it involves neither arachidonic acid metabolism nor protein kinase C activation. The time course of OAG-induced 45Ca release, which was slower than IP3-induced 45Ca release, corresponded to the time course of conversion of the OAG to 1-oleoyl-2-acetoyl phosphatidic acid (OAG-PA). When either OAG-PA or lysophosphatidic acid was added to the saponin-treated platelets, the extent of 45Ca release was similar to that observed with OAG, but both the OAG-PA and the lysophosphatidic acid were 5 to 10 times more potent than OAG on a molar basis. These data suggest: (1) that the Ca release caused by diacylglycerol is actually due to formation of phosphatidic acid and/or lysophosphatidic acid, (2) that these molecules are not acting as simple Ca ionophores and (3) that diacylglycerol metabolites may augment the changes in Ca homeostasis caused by IP3 during platelet activation.

UR - http://www.scopus.com/inward/record.url?scp=0023127874&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0023127874&partnerID=8YFLogxK

U2 - 10.1016/0006-291X(87)90444-X

DO - 10.1016/0006-291X(87)90444-X

M3 - Article

C2 - 3493001

AN - SCOPUS:0023127874

VL - 142

SP - 7

EP - 14

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

SN - 0006-291X

IS - 1

ER -