|
|
Blood, 1 December 2004, Vol. 104, No. 12, pp. 3603-3610.
Prepublished online as a Blood First Edition Paper on August 5, 2004; DOI 10.1182/blood-2003-12-4330.
 Previous Article | Table of Contents | Next Article 
HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY
The nucleotide transporter MRP4 (ABCC4) is highly expressed in human platelets and present in dense granules, indicating a role in mediator storage
Gabriele Jedlitschky,
Konstanze Tirschmann,
Lena E. Lubenow,
Hendrik K. Nieuwenhuis,
Jan W. N. Akkerman,
Andreas Greinacher, and
Heyo K. Kroemer
From the Department of Pharmacology, Peter Holtz Research Center of Pharmacology and Experimental Therapeutics, Greifswald, Germany; the Department of Immunology and Transfusion Medicine, Ernst-Moritz-Arndt-University, Greifswald, Germany; and the Department of Haematology, University Medical Centre Utrecht, Utrecht, the Netherlands.
Platelet aggregation is initiated by the release of mediators as adenosine diphosphate (ADP) stored in platelet granules. Possible candidates for transport proteins mediating accumulation of these mediators in granules include multidrug resistance protein 4 (MRP4, ABCC4), a transport pump for cyclic nucleotides and nucleotide analogs. We investigated the expression of MRP4 in human platelets by immunoblotting, detecting a strong signal at 170 kDa. Immunofluorescence microscopy using 2 MRP4-specific antibodies revealed staining mainly in intracellular structures, which largely colocalized with the accumulation of mepacrine as marker for delta-granules and to a lower extent at the plasma membrane. Furthermore, an altered distribution of MRP4 was observed in platelets from a patient with Hermansky-Pudlak syndrome with defective delta-granules. Adenosine triphosphate (ATP)–dependent cyclic guanosine monophosphate (cGMP) transport codistributed with MRP4 detection in subcellular fractions, with highest activities in the dense granule and plasma membrane fractions. This transport was inhibited by dipyramidole, indomethacin, and MK571 with median inhibitory concentration (IC50) values of 12, 22, and 43 µM, and by ibuprofen. Transport studies with [3H]ADP indicated the presence of an orthovanadate-sensitive ADP transporting system, inhibited by dipyramidole, MK571, and cyclic nucleotides. The results indicate a function of MRP4 in platelet mediator storage and inhibition of MRP4 may represent a novel mechanism for inhibition of platelet function by some anti-inflammatory drugs.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
J. M. Evans, J. P. Day, P. Cabrero, J. A. T. Dow, and S.-A. Davies
A new role for a classical gene: White transports cyclic GMP
J. Exp. Biol.,
March 15, 2008;
211(6):
890 - 899.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Rius, J. Hummel-Eisenbeiss, and D. Keppler
ATP-Dependent Transport of Leukotrienes B4 and C4 by the Multidrug Resistance Protein ABCC4 (MRP4)
J. Pharmacol. Exp. Ther.,
January 1, 2008;
324(1):
86 - 94.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Currie, B. King, A. L. Lawrenson, L. K. Schroeder, A. M. Kershner, and G. J. Hermann
Role of the Caenorhabditis elegans Multidrug Resistance Gene, mrp-4, in Gut Granule Differentiation
Genetics,
November 1, 2007;
177(3):
1569 - 1582.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. K. Schroeder, S. Kremer, M. J. Kramer, E. Currie, E. Kwan, J. L. Watts, A. L. Lawrenson, and G. J. Hermann
Function of the Caenorhabditis elegans ABC Transporter PGP-2 in the Biogenesis of a Lysosome-related Fat Storage Organelle
Mol. Biol. Cell,
March 1, 2007;
18(3):
995 - 1008.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. L. Dudas, R. M. Pelis, E. J. Braun, and J. L. Renfro
Transepithelial urate transport by avian renal proximal tubule epithelium in primary culture
J. Exp. Biol.,
November 15, 2005;
208(22):
4305 - 4315.
[Abstract]
[Full Text]
[PDF]
|
|
|
| |
