Expression profiles of 50 xenobiotic transporter genes in humans and pre-clinical species: a resource for investigations into drug disposition.
Carrier-mediated transporters play a critical role in xenobiotic disposition and transporter research is complicated by species differences and their selective tissue expression. The purpose of this study was to generate a comprehensive data set of xenobiotic transporter gene expression profiles in humans and the pre-clinical species mouse, rat, beagle dog and cynomolgus monkey. mRNA expression profiles of 50 genes from the ABC, SLC and SLCO transporter superfamilies were examined in 40 human tissues by microarray analyses. Transporter genes that were identified as enriched in the liver or kidney, or that were selected for their known roles in xenobiotic disposition, were then compared in 22 tissues across the five species. Finally, as clinical variability in drug response and adverse reactions may be the result of variability in transporter gene expression, variability in the expression of selected transporter genes in 75 human liver donors were examined and compared with the highly variable drug metabolizing enzyme CYP3A4.
Bleasby
K
K
Department of Drug Metabolism, Merck Research Laboratories, Rahway, NJ 07065, USA. kelly_bleasby@merck.com
Castle
J C
JC
Roberts
C J
CJ
Cheng
C
C
Bailey
W J
WJ
Sina
J F
JF
Kulkarni
A V
AV
Hafey
M J
MJ
Evers
R
R
Johnson
J M
JM
Ulrich
R G
RG
Slatter
J G
JG
D000818:Animals; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D008658:Inactivation, Metabolic; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D013045:Species Specificity; D014019:Tissue Donors; D015262:Xenobiotics / Q000378:metabolism*
D026901:Membrane Transport Proteins; D015262:Xenobiotics