Expression ofABC Transporters Along Human Small Intestine
Transporter proteins play a large role in the absorption, disposition, excretion and toxicity of many therapeutic drugs. This is supported by the fact that many known drugs are substrates for transporter protein. Therefore, the expression of transporters is important in knowing possible drug-drug interactions, a critical aspect of the drug discovery process. Transporter proteins are expressed in various parts of the body but those expressed in the small intestine can greatly affect the bioavailability of orally administered drugs. Specifically, adenosine triphosphate binding cassette (ABC) transporters greatly reduced the permeability of orally administered drugs by an "efflux" mechanism. Of the ABC transporters, p-glycoprotein has been the most widely studied and understood transporter protein. The majority of work done to date has examined the expression patterns at the protein level in animal models or at the mRNA level in human models. In this study the expression of p-glycoprotein, breast cancer resistance protein (Bcrp), and multidrug resistance-associated protein 2 (Mrp2) were examined in human models at the protein level using western blot analysis. The expression profile was examined along the entire length of the small intestine from the duodenum to the ileum. The results indicate that the expression of P-gp increases toward the distal regions of the small intestine. The expression of Bcrp showed great intervariability but showed the highest expression in distal regions. Lastly, Mrp2 expression was unsuccessfully detected in all of the human intestinal samples.