Intestinal membrane transport of drugs and nutrients: genomics of membrane transporters using expression microarrays.
Carrier-mediated transport across membranes plays an important role in drug and nutrient absorption. However, relevant transporters remain largely unknown for most substrates. Their identification requires global analysis of expressed mRNAs in intestinal tissues. Microarray technologies capable of measuring mRNA profiles have proven useful in detecting the expression of genes encoding transporters and ion channels in intestines and Caco-2 cells. This colon carcinoma cell line with characteristics of absorptive enterocytes serves as a common model for drug absorption studies. Gene expression patterns of membrane transporters and channels define the cell's overall transport capacity. Moreover, transporter mRNA profiles provide a basis for assessing drug-drug and drug-food interactions in intestinal absorption. To determine relevant transporters for any given substrate, chemogenomic methods have emerged correlating mRNA expression in multiple tissues to drug transport or response. The resultant drug-transporter databases permit the search for transporter-drug relationships at a genomic scale.
Anderle
Pascale
P
ISREC, Chemin des Boveresses 155, 1066 Epalinges s/Lausanne, Switzerland. pascale.anderle@isrec.unil.ch
Huang
Ying
Y
Sadée
Wolfgang
W
D000818:Animals; D001692:Biological Transport / Q000235:genetics; D018565:Food-Drug Interactions / Q000235:genetics; D023281:Genomics / Q000379:methods; D006801:Humans; D007408:Intestinal Absorption / Q000235:genetics*; D026901:Membrane Transport Proteins / Q000096:biosynthesis / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D004364:Pharmaceutical Preparations / Q000378:metabolism*
D026901:Membrane Transport Proteins; D004364:Pharmaceutical Preparations