First Name:
Caitlin
Last Name:
Covington
Major Department:
Chemistry
Thesis Director:
Jennifer Cecile
Date of Thesis:
May 2012
Organic cation transporters (OCTs) are studied for their excretion of metabolic and xenobiotic cations. The nematode Caenorhabditis elegans (C. elegans) is a model system employed to study the mammalian OCT. In this work, a phylogenie tree was constructed to compare the human and C. elegans OCTs (CeOCTs). Despite low sequence homology(~ 28%) between the CeOCT and human OCTs (hOCTs), previous work has illustrated common substrates. To further characterize the CeOCT, a fluorescent assay using the nematodes was developed to determine additional substrates and inhibitors. Further, glucose trials were performed to test the effects of glucose treatment on the uptake of the fluorescent substrate quinacrine. Fluorescence microscopy illustrated uptake of quinacrine in areas surrounding the lumen of the C. elegans intestine. Replicated time trials revealed that five minute incubation with quinacrine is sufficient for the functional assay. Current results have not shown effective inhibition by tetramethylammonium cation (TMA), quercetin, or rutin. Data from the glucose assays did not reveal a significant increase in uptake (p>0.05), although the results are promising. Future studies will be performed with more potent inhibitors, including tetraethylammonium cation (TEA) and 1-methyl-4-phenylpyridinium (MPP+). Future studies will also assess an OCT knockout strain of the C. elegans and a liquid C. elegans culture for greater assay efficiency.