RT Journal Article
SR Electronic
T1 Interindividual Variability and Tissue-Specificity in the Expression of Cytochrome P450 3A mRNA
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 1108
OP 1114
DO 10.1124/dmd.30.10.1108
VO 30
IS 10
A1 Koch, Ina
A1 Weil, Regina
A1 Wolbold, Renzo
A1 Brockmöller, Jürgen
A1 Hustert, Elisabeth
A1 Burk, Oliver
A1 Nuessler, Andreas
A1 Neuhaus, Peter
A1 Eichelbaum, Michel
A1 Zanger, Ulrich
A1 Wojnowski, Leszek
YR 2002
UL http://dmd.aspetjournals.org/content/30/10/1108.abstract
AB The elucidation of the individual contributions of the fourCYP3A genes to the overall CYP3A activity has been hampered by similarities in their sequence and function. We investigated the expression of CYP3A mRNA species in the liver and in various other tissues using gene-specific TaqMan probes. CYP3A4 transcripts were the most abundant CYP3A mRNA in each of the 63 white European livers tested and accounted on average for 95% of the combined CYP3A mRNA pool. CYP3A5 and CYP3A7 each contributed on average 2%, whereas CYP3A43 contributed 0.3% transcripts to this pool. Fourteen percent of livers exhibited an increased share of CYP3A5 transcripts (range 4–20%). These livers were either heterozygous for the marker of the CYP3A5 polymorphism, the CYP3A5*1A allele, or expressed very low levels of CYP3A4 mRNA. The CYP3A7 expression was bimodal, and it was increased in 15% livers. CYP3A4 was the dominant CYP3A in the intestine, followed by CYP3A5. CYP3A5 and CYP3A7, but not CYP3A4, were also expressed in the adrenal gland and in the prostate, whereas only CYP3A5 was detected in the kidney. These three tissues were shown to express much lower levels of pregnane X receptor mRNA than the intestine, indicating possibly a different mode of regulation of CYP3A expression. Expression of CYP3A genes was undetectable in peripheral blood lymphocytes. In summary, these assays and results should aid in our efforts to further dissect the regulation and the physiological and pharmacological significance of CYP3A isozymes. The American Society for Pharmacology and Experimental Therapeutics