Proteomic profiling of drug and nutrient transporter expression by small intestinal region in neonates, pediatrics, and adults

Abstract

Transporters localized to the small intestinal epithelium govern the absorption of many orally administered drugs and nutrients, and thorough characterization of transporter protein abundance is key to accurate prediction of small molecule absorption. Previous studies have reported more than 100 solute carrier and ATP-binding cassette superfamilies expressed in the intestine, but only a small subset of these transporter proteins have been quantified in native intestinal tissue. In addition, a majority of published transporter abundance data for the intestine was collected with adult tissue. Here, we report the identification and relative quantification of 87 solute carrier and 18 ATP-binding cassette superfamily transporters by intestinal region in neonatal, pediatric, and adult small intestinal mucosa using data-independent acquisition mass spectrometry. This study identified transporters uniquely expressed by intestinal region in all three age groups and region-associated abundance for 23 SLC/ABC transporters in pediatrics and adults. The protein abundance data reported here provide a valuable resource for the prediction of nutrient and drug absorption and efflux across age and will inform future studies of specific transporters and age-associated differences in transporter abundance. Significance statementWe report the relative abundance of key xenobiotic transporters along the length of the small intestine in neonates, pediatrics, and adults based on data-independent acquisition mass spectrometry. Intestinal region-associated transporter expression was observed for drug transporters and under-studied nutrient transporters across age groups.