PMID- 10064732
OWN - NLM
STAT- MEDLINE
DCOM- 19990413
LR  - 20171116
IS  - 0022-2275 (Print)
IS  - 0022-2275 (Linking)
VI  - 40
IP  - 3
DP  - 1999 Mar
TI  - Characterization of a leukotriene C4 export mechanism in human platelets:
      possible involvement of multidrug resistance-associated protein 1.
PG  - 439-46
AB  - Platelets express leukotriene (LT) C4 synthase and can thus participate in the
      formation of bioactive LTC4. To further elucidate the relevance of this
      capability, we have now determined the capacity of human platelets to export
      LTC4. Endogenously formed LTC4 was efficiently released from human platelets
      after incubation with LTA4 at 37 degrees C, whereas only 15% of produced LTC4 was
      exported when the cells were incubated at 0 degrees C. The activation energy of
      the process was calculated to 49.9 +/- 7.7 kJ/mol, indicating carrier-mediated
      LTC4 export. This was also supported by the finding that the transport was
      saturable, reaching a maximal export rate of 470 +/- 147 pmol LTC4/min x 10(9)
      platelets. Furthermore, markedly suppressed LTC4 transport was induced by a
      combination of the metabolic inhibitors antimycin A and 2-deoxyglucose,
      suggesting energy-dependent export. The presence in platelets of multidrug
      resistance-associated protein 1 (MRP1), a protein described to be an
      energy-dependent LTC4 transporter in various cell types, was demonstrated at the 
      mRNA and protein level. Additional support for a role of MRP1 in platelet LTC4
      export was obtained by the findings that the process was inhibited by probenecid 
      and the 5-lipoxygenase-activating protein (FLAP) inhibitor, MK-886. The present
      findings further support the physiological relevance of platelet LTC4 production.
FAU - Sjolinder, M
AU  - Sjolinder M
AD  - Department of Medical Biochemistry and Biophysics, Division of Physiological
      Chemistry II, Karolinska Institutet, S-171 77 Stockholm, Sweden.
FAU - Tornhamre, S
AU  - Tornhamre S
FAU - Claesson, H E
AU  - Claesson HE
FAU - Hydman, J
AU  - Hydman J
FAU - Lindgren, J
AU  - Lindgren J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Lipid Res
JT  - Journal of lipid research
JID - 0376606
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Indoles)
RN  - 0 (Leukotriene A4)
RN  - 0 (Lipoxygenase Inhibitors)
RN  - 0 (MSH3 protein, human)
RN  - 0 (Multidrug Resistance-Associated Proteins)
RN  - 0 (MutS Homolog 3 Protein)
RN  - 0 (RNA, Messenger)
RN  - 080626SQ8C (MK-886)
RN  - 2CU6TT9V48 (Leukotriene C4)
RN  - 642-15-9 (Antimycin A)
RN  - 9G2MP84A8W (Deoxyglucose)
RN  - PO572Z7917 (Probenecid)
RN  - Y49M64GZ4Q (multidrug resistance-associated protein 1)
SB  - IM
MH  - Antimycin A/pharmacology
MH  - Biological Transport
MH  - Blood Platelets/*metabolism
MH  - DNA-Binding Proteins/genetics/*metabolism
MH  - Deoxyglucose/pharmacology
MH  - Humans
MH  - Indoles/pharmacology
MH  - Kinetics
MH  - Leukotriene A4/metabolism
MH  - Leukotriene C4/*pharmacokinetics
MH  - Lipoxygenase Inhibitors/pharmacology
MH  - *Multidrug Resistance-Associated Proteins
MH  - MutS Homolog 3 Protein
MH  - Probenecid/pharmacology
MH  - RNA, Messenger/metabolism
MH  - Temperature
EDAT- 1999/03/05 00:00
MHDA- 1999/03/05 00:01
CRDT- 1999/03/05 00:00
PHST- 1999/03/05 00:00 [pubmed]
PHST- 1999/03/05 00:01 [medline]
PHST- 1999/03/05 00:00 [entrez]
PST - ppublish
SO  - J Lipid Res. 1999 Mar;40(3):439-46.