Effects of dietary salt on the expression of drug transporters, cytochrome P4503a, and nuclear receptors in rats.
Quantitative reverse-transcription polymerase chain reaction (RT-PCR) and Western blot analyses were carried out to investigate the regulation of genes responsible for the transport and metabolism of drugs in response to different levels of salt intake. A high-salt diet compared with medium- and low-salt diets reduced the expression levels of the mdr1a and mdr1b genes in the liver and kidney, but increased their expression levels in the duodenum, jejunum, and ileum. Likewise, the expression levels of other transporters and CYP3a3 genes varied in different tissues. The expression levels of nuclear receptors, such as Pxr, Fxr, and Car, were also modulated differently in the liver, kidney, and intestines. The protein levels of Mdr1, Oct1, CYP3a, Pxr, Fxr, and Car were correlated with the changes in mRNA levels of the respective genes. In conclusion, the changes in the expression of drug transporters, metabolic enzymes, and nuclear receptors were tissue specific.
Kang
H J
HJ
Department of Pharmacology and PharmacoGenomics Research Center, Inje University College of Medicine, Busan, Korea.
Song
I S
IS
Lee
S S
SS
Yoo
M A
MA
Shin
J G
JG
D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D051544:Cytochrome P-450 CYP3A / Q000235:genetics / Q000378:metabolism*; D007082:Ileum / Q000187:drug effects; D007668:Kidney / Q000187:drug effects; D008099:Liver / Q000187:drug effects; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D017673:Sodium Chloride, Dietary / Q000494:pharmacology*
D018528:ATP-Binding Cassette Transporters; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D017673:Sodium Chloride, Dietary; D051544:Cytochrome P-450 CYP3A