Organic Anion Transport in Caenorhabditis elegans

Abstract

Organic anion transporters (OATs) aid in the elimination of negatively charged drugs and xenobiotics from the body through excretory organs such as the intestine, liver and kidney. The nonmammalian Caenorhabditis elegans (C. elegans) nematode contains one OAT isoform (CeOAT1) with sequence homology and overlapping substrate specificity to mammalian OATs. In this work, fluorescence microscopy illustrates accumulation of the organic anion fluorescein in the intestinal lumen of the wild‐type C. elegans (strain N2) and in intestinal cells in the efflux transporter knockout (strain NL152 which lacks p‐glycoprotein isoforms 1 and 3 and the multidrug resistance‐associated protein isoform 1). CeOAT1 function is investigated by quantifying fluorescein uptake in C. elegans strain NL152 with fluorescence microscopy or a fluorescence plate reader in the presence of nonfluorescent anions. Pre‐treatment with probenecid, p‐aminohippurate or folate inhibits fluorescein uptake while pretreatment with the dicarboxylate fumerate stimulates fluorescein uptake. Both agar and liquid nematode culture are amenable to these experiments and synchronized cultures provide insight into CeOAT1 function at specific life stages. These in vivo results suggest the C. elegans nematode is a model organism to examine mammalian OAT function. This research was supported by Appalachian State University.