RT Journal Article
SR Electronic
T1 Localization of Multidrug Resistance-Associated Proteins along the Blood-Testis Barrier in Rat, Macaque, and Human Testis
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 89
OP 93
DO 10.1124/dmd.113.054577
VO 42
IS 1
A1 David M. Klein
A1 Stephen H. Wright
A1 Nathan J. Cherrington
YR 2014
UL http://dmd.aspetjournals.org/content/42/1/89.abstract
AB The blood-testis barrier (BTB) prevents the entry of many drugs into seminiferous tubules, which can be beneficial for therapy not intended for the testis but may decrease drug efficacy for medications requiring entry to the testis. Previous data have 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 physiologic 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 the testis, namely, MRP1, MRP4, MRP5, and MRP8, 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 nonhuman 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 may limit drug disposition into seminiferous tubules, as may MRP4 in human and nonhuman primates but not in rats. These data also suggest that MRP5 and MRP8 may not have a major impact on the penetration of drugs across the BTB.