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PMID:24130369
| Citation |
'Klein, DM, Wright, SH and Cherrington, NJ (2013) Localization of Multidrug Resistance-Associated Proteins Along the Blood-testis Barrier in Rat, Macaque, and Human Testis. Drug Metab. Dispos. ' |
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| Abstract |
The blood-testis barrier (BTB) prevents the entry of many drugs into seminiferous tubules thereby decreasing their efficacy. Previous data has shown that some of the transporters in the multidrug resistance-associated protein (MRP) family (ABCC) are expressed in the testis. By determining the subcellular localization of these transporters, their physiological function and effect on drug disposition may be better predicted. Using immunohistochemistry (IHC), we determined the site of expression of the MRP transporters expressed in testis, namely MRP1, MRP4, MRP5 and MRP8, in testis from immature and mature rats, rhesus macaques, and adult humans. We determined that in all species MRP1 was restricted to the basolateral membrane of Sertoli cells, MRP5 is located in Leydig cells, and MRP8 is located in round spermatids, whereas MRP4 showed species specific localization. MRP4 is expressed on the basolateral membrane of Sertoli cells in human and non-human primates, but on the apical membrane of Sertoli cells in immature and mature rats, representing a potential caution when using rat models as a means for studying drug disposition across the BTB. These data suggest that MRP1 acts as an obstacle in drug disposition into seminiferous tubules, as does MRP4 in human and non-human primates but not in rats. These data also suggest that MRP5 and MRP8 do not have a major impact on the penetration of drugs across the BTB. |
| Links |
PubMed Online version:10.1124/dmd.113.054577 |
| Keywords |
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| edit table |
Significance
Annotations
| Gene product | Qualifier | GO Term | Evidence Code | with/from | Aspect | Extension | Notes | Status |
|---|---|---|---|---|---|---|---|---|
|
part_of |
GO:0016323: basolateral plasma membrane |
ECO:0000314: direct assay evidence used in manual assertion |
C |
Seeded From UniProt |
complete | |||
| GO:0016323: basolateral plasma membrane |
ECO:0000314: |
C |
Figure 1 |
complete | ||||
|
part_of |
GO:0016323: basolateral plasma membrane |
ECO:0000314: direct assay evidence used in manual assertion |
C |
Seeded From UniProt |
complete | |||
| GO:0016323: basolateral plasma membrane |
ECO:0000314: |
C |
Figure 1 A and B. |
complete | ||||
|
part_of |
GO:0016324: apical plasma membrane |
ECO:0000314: direct assay evidence used in manual assertion |
C |
Seeded From UniProt |
complete | |||
| GO:0016324: apical plasma membrane |
ECO:0000314: |
C |
Figure 2A and 2B |
complete | ||||
| GO:0016323: basolateral plasma membrane |
ECO:0000314: |
C |
Figure 2D |
complete | ||||
|
part_of |
GO:0016323: basolateral plasma membrane |
ECO:0000314: direct assay evidence used in manual assertion |
C |
Seeded From UniProt |
complete | |||
See also
References
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