schliessen

Filtern

 

Bibliotheken

Mechanism of rapid elimination of lysophosphatidic acid and related lipids from the circulation of mice.

Lysophosphatidic acid (LPA) is a bioactive lipid mediator. Concentrations of the major LPA species in mouse plasma decreased uniformly following administration of a potent selective inhibitor of the LPA-generating lysophospholipase D autotaxin, identifying an active mechanism for removal of LPA from... Full description

Journal Title: Journal of lipid research October 2013, Vol.54(10), pp.2775-2784
Main Author: Salous, Abdel K
Other Authors: Panchatcharam, Manikandan , Sunkara, Manjula , Mueller, Paul , Dong, Anping , Wang, Yuhuan , Graf, Gregory A , Smyth, Susan S , Morris, Andrew J
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: E-ISSN: 1539-7262 ; DOI: 10.1194/jlr.M039685
Link: http://search.proquest.com/docview/1432620893/?pq-origsite=primo
Zum Text:
SendSend as email Add to Book BagAdd to Book Bag
Staff View
recordid: proquest1432620893
title: Mechanism of rapid elimination of lysophosphatidic acid and related lipids from the circulation of mice.
format: Article
creator:
  • Salous, Abdel K
  • Panchatcharam, Manikandan
  • Sunkara, Manjula
  • Mueller, Paul
  • Dong, Anping
  • Wang, Yuhuan
  • Graf, Gregory A
  • Smyth, Susan S
  • Morris, Andrew J
subjects:
  • Animals–Pharmacology
  • Benzoxazoles–Metabolism
  • Cells, Cultured–Metabolism
  • Half-Life–Blood
  • Hepatocytes–Pharmacokinetics
  • Lipid Metabolism–Pharmacology
  • Liver–Metabolism
  • Lysophospholipids–Pharmacology
  • Male–Pharmacology
  • Mice–Pharmacology
  • Mice, Inbred C57bl–Pharmacology
  • Phosphodiesterase Inhibitors–Pharmacology
  • Phosphoric Diester Hydrolases–Pharmacology
  • Piperazines–Pharmacology
  • Tandem Mass Spectrometry–Pharmacology
  • Tissue Distribution–Pharmacology
  • 6-(3-(Piperazin-1-Yl)Propanoyl)Benzo(D)Oxazol-2(3h)-One
  • Benzoxazoles
  • Lysophospholipids
  • Phosphodiesterase Inhibitors
  • Piperazines
  • Phosphoric Diester Hydrolases
  • Alkylglycerophosphoethanolamine Phosphodiesterase
  • Lysophosphatidic Acid
  • Autotaxin
  • Lipid Phosphate Phosphatase
  • Mass Spectrometry
  • Transcellular Uptake
ispartof: Journal of lipid research, October 2013, Vol.54(10), pp.2775-2784
description: Lysophosphatidic acid (LPA) is a bioactive lipid mediator. Concentrations of the major LPA species in mouse plasma decreased uniformly following administration of a potent selective inhibitor of the LPA-generating lysophospholipase D autotaxin, identifying an active mechanism for removal of LPA from the circulation. LPA, akylglycerol phosphate (AGP), sphingosine 1-phosphate (S1P), and a variety of structural mimetics of these lipids, including phosphatase-resistant phosphonate analogs of LPA, were rapidly eliminated (t1/2 < 30 s) from the circulation of mice following intravenous administration of a single bolus dose without significant metabolism in situ in the blood. These lipids accumulated in the liver. Elimination of intravenously administered LPA was blunted by ligation of the hepatic circulation, and ∼90% of LPA administered through the portal vein was accumulated by the isolated perfused mouse liver at first pass. At early times following intravenous administration, more LPA was associated with a nonparenchymal liver cell fraction than with hepatocytes. Primary cultures of nonparenchymal liver cells rapidly assimilated exogenously provided LPA. Our results identify hepatic uptake as an important determinant of the bioavailability of LPA and bioactive lysophospholipid mimetics and suggest a mechanism to explain changes in circulating LPA levels that have been associated with liver dysfunction in humans.
language: eng
source:
identifier: E-ISSN: 1539-7262 ; DOI: 10.1194/jlr.M039685
fulltext: fulltext
issn:
  • 15397262
  • 1539-7262
url: Link


@attributes
ID1785038806
RANK0.07
NO1
SEARCH_ENGINEprimo_central_multiple_fe
SEARCH_ENGINE_TYPEPrimo Central Search Engine
LOCALfalse
PrimoNMBib
record
control
sourcerecordid1432620893
sourceidproquest
recordidTN_proquest1432620893
sourcesystemPC
pqid1432620893
display
typearticle
titleMechanism of rapid elimination of lysophosphatidic acid and related lipids from the circulation of mice.
creatorSalous, Abdel K ; Panchatcharam, Manikandan ; Sunkara, Manjula ; Mueller, Paul ; Dong, Anping ; Wang, Yuhuan ; Graf, Gregory A ; Smyth, Susan S ; Morris, Andrew J
contributorSalous, Abdel K (correspondence author) ; Salous, Abdel K (record owner)
ispartofJournal of lipid research, October 2013, Vol.54(10), pp.2775-2784
identifierE-ISSN: 1539-7262 ; DOI: 10.1194/jlr.M039685
subjectAnimals–Pharmacology ; Benzoxazoles–Metabolism ; Cells, Cultured–Metabolism ; Half-Life–Blood ; Hepatocytes–Pharmacokinetics ; Lipid Metabolism–Pharmacology ; Liver–Metabolism ; Lysophospholipids–Pharmacology ; Male–Pharmacology ; Mice–Pharmacology ; Mice, Inbred C57bl–Pharmacology ; Phosphodiesterase Inhibitors–Pharmacology ; Phosphoric Diester Hydrolases–Pharmacology ; Piperazines–Pharmacology ; Tandem Mass Spectrometry–Pharmacology ; Tissue Distribution–Pharmacology ; 6-(3-(Piperazin-1-Yl)Propanoyl)Benzo(D)Oxazol-2(3h)-One ; Benzoxazoles ; Lysophospholipids ; Phosphodiesterase Inhibitors ; Piperazines ; Phosphoric Diester Hydrolases ; Alkylglycerophosphoethanolamine Phosphodiesterase ; Lysophosphatidic Acid ; Autotaxin ; Lipid Phosphate Phosphatase ; Mass Spectrometry ; Transcellular Uptake
languageeng
source
descriptionLysophosphatidic acid (LPA) is a bioactive lipid mediator. Concentrations of the major LPA species in mouse plasma decreased uniformly following administration of a potent selective inhibitor of the LPA-generating lysophospholipase D autotaxin, identifying an active mechanism for removal of LPA from the circulation. LPA, akylglycerol phosphate (AGP), sphingosine 1-phosphate (S1P), and a variety of structural mimetics of these lipids, including phosphatase-resistant phosphonate analogs of LPA, were rapidly eliminated (t1/2 < 30 s) from the circulation of mice following intravenous administration of a single bolus dose without significant metabolism in situ in the blood. These lipids accumulated in the liver. Elimination of intravenously administered LPA was blunted by ligation of the hepatic circulation, and ∼90% of LPA administered through the portal vein was accumulated by the isolated perfused mouse liver at first pass. At early times following intravenous administration, more LPA was associated with a nonparenchymal liver cell fraction than with hepatocytes. Primary cultures of nonparenchymal liver cells rapidly assimilated exogenously provided LPA. Our results identify hepatic uptake as an important determinant of the bioavailability of LPA and bioactive lysophospholipid mimetics and suggest a mechanism to explain changes in circulating LPA levels that have been associated with liver dysfunction in humans.
version3
lds50peer_reviewed
links
openurl$$Topenurl_article
openurlfulltext$$Topenurlfull_article
backlink$$Uhttp://search.proquest.com/docview/1432620893/?pq-origsite=primo$$EView_record_in_ProQuest_(subscribers_only)
search
creatorcontrib
0Salous, Abdel K
1Panchatcharam, Manikandan
2Sunkara, Manjula
3Mueller, Paul
4Dong, Anping
5Wang, Yuhuan
6Graf, Gregory A
7Smyth, Susan S
8Morris, Andrew J
titleMechanism of rapid elimination of lysophosphatidic acid and related lipids from the circulation of mice.
subject
0Animals–Pharmacology
1Benzoxazoles–Metabolism
2Cells, Cultured–Metabolism
3Half-Life–Blood
4Hepatocytes–Pharmacokinetics
5Lipid Metabolism–Pharmacology
6Liver–Metabolism
7Lysophospholipids–Pharmacology
8Male–Pharmacology
9Mice–Pharmacology
10Mice, Inbred C57bl–Pharmacology
11Phosphodiesterase Inhibitors–Pharmacology
12Phosphoric Diester Hydrolases–Pharmacology
13Piperazines–Pharmacology
14Tandem Mass Spectrometry–Pharmacology
15Tissue Distribution–Pharmacology
166-(3-(Piperazin-1-Yl)Propanoyl)Benzo(D)Oxazol-2(3h)-One
17Benzoxazoles
18Lysophospholipids
19Phosphodiesterase Inhibitors
20Piperazines
21Phosphoric Diester Hydrolases
22Alkylglycerophosphoethanolamine Phosphodiesterase
23Lysophosphatidic Acid
24Autotaxin
25Lipid Phosphate Phosphatase
26Mass Spectrometry
27Transcellular Uptake
28autotaxin
29lipid phosphate phosphatase
30mass spectrometry
31transcellular uptake
general
0English
110.1194/jlr.M039685
2MEDLINE (ProQuest)
3ProQuest Biological Science Collection
4ProQuest Natural Science Collection
5ProQuest SciTech Collection
6Biological Science Database
7Natural Science Collection
8SciTech Premium Collection
9Health Research Premium Collection
10Health Research Premium Collection (Alumni edition)
11Biological Science Index (ProQuest)
sourceidproquest
recordidproquest1432620893
issn
015397262
11539-7262
rsrctypearticle
creationdate2013
addtitleJournal of lipid research
searchscope
01007527
11007944
21009130
310000004
410000038
510000050
610000120
710000159
810000238
910000253
1010000260
1110000270
1210000271
1310000302
1410000350
15proquest
scope
01007527
11007944
21009130
310000004
410000038
510000050
610000120
710000159
810000238
910000253
1010000260
1110000270
1210000271
1310000302
1410000350
15proquest
lsr43
01007527false
11007944false
21009130false
310000004false
410000038false
510000050false
610000120false
710000159false
810000238false
910000253false
1010000260false
1110000270false
1210000271false
1310000302false
1410000350false
contributorSalous, Abdel K
startdate20131001
enddate20131001
citationpf 2775 pt 2784 vol 54 issue 10
lsr30VSR-Enriched:[pqid, description, issn]
sort
titleMechanism of rapid elimination of lysophosphatidic acid and related lipids from the circulation of mice.
authorSalous, Abdel K ; Panchatcharam, Manikandan ; Sunkara, Manjula ; Mueller, Paul ; Dong, Anping ; Wang, Yuhuan ; Graf, Gregory A ; Smyth, Susan S ; Morris, Andrew J
creationdate20131001
lso0120131001
facets
frbrgroupid8411614608454486823
frbrtype5
newrecords20181218
languageeng
creationdate2013
topic
0Animals–Pharmacology
1Benzoxazoles–Metabolism
2Cells, Cultured–Metabolism
3Half-Life–Blood
4Hepatocytes–Pharmacokinetics
5Lipid Metabolism–Pharmacology
6Liver–Metabolism
7Lysophospholipids–Pharmacology
8Male–Pharmacology
9Mice–Pharmacology
10Mice, Inbred C57bl–Pharmacology
11Phosphodiesterase Inhibitors–Pharmacology
12Phosphoric Diester Hydrolases–Pharmacology
13Piperazines–Pharmacology
14Tandem Mass Spectrometry–Pharmacology
15Tissue Distribution–Pharmacology
166-(3-(Piperazin-1-Yl)Propanoyl)Benzo(D)Oxazol-2(3h)-One
17Benzoxazoles
18Lysophospholipids
19Phosphodiesterase Inhibitors
20Piperazines
21Phosphoric Diester Hydrolases
22Alkylglycerophosphoethanolamine Phosphodiesterase
23Lysophosphatidic Acid
24Autotaxin
25Lipid Phosphate Phosphatase
26Mass Spectrometry
27Transcellular Uptake
collection
0MEDLINE (ProQuest)
1ProQuest Biological Science Collection
2ProQuest Natural Science Collection
3ProQuest SciTech Collection
4Biological Science Database
5Natural Science Collection
6SciTech Premium Collection
7Health Research Premium Collection
8Health Research Premium Collection (Alumni edition)
9Biological Science Index (ProQuest)
prefilterarticles
rsrctypearticles
creatorcontrib
0Salous, Abdel K
1Panchatcharam, Manikandan
2Sunkara, Manjula
3Mueller, Paul
4Dong, Anping
5Wang, Yuhuan
6Graf, Gregory A
7Smyth, Susan S
8Morris, Andrew J
jtitleJournal of lipid research
toplevelpeer_reviewed
delivery
delcategoryRemote Search Resource
fulltextfulltext
addata
aulast
0Salous
1Panchatcharam
2Sunkara
3Mueller
4Dong
5Wang
6Graf
7Smyth
8Morris
aufirst
0Abdel K
1Manikandan
2Manjula
3Paul
4Anping
5Yuhuan
6Gregory A
7Susan S
8Andrew J
au
0Salous, Abdel K
1Panchatcharam, Manikandan
2Sunkara, Manjula
3Mueller, Paul
4Dong, Anping
5Wang, Yuhuan
6Graf, Gregory A
7Smyth, Susan S
8Morris, Andrew J
addauSalous, Abdel K
atitleMechanism of rapid elimination of lysophosphatidic acid and related lipids from the circulation of mice.
jtitleJournal of lipid research
risdate20131001
volume54
issue10
spage2775
epage2784
pages2775-2784
eissn1539-7262
formatjournal
genrearticle
ristypeJOUR
doi10.1194/jlr.M039685
urlhttp://search.proquest.com/docview/1432620893/
issn00222275
date2013-10-01