Investigations of Serotonin Metabolism in Mammalian and Other Deuterostome Model Systems
Squires, Leah N.
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https://hdl.handle.net/2142/84282
Description
Title
Investigations of Serotonin Metabolism in Mammalian and Other Deuterostome Model Systems
Author(s)
Squires, Leah N.
Issue Date
2007
Doctoral Committee Chair(s)
Jonathan Sweedler
Department of Study
Chemistry
Discipline
Chemistry
Degree Granting Institution
University of Illinois at Urbana-Champaign
Degree Name
Ph.D.
Degree Level
Dissertation
Keyword(s)
Chemistry, Analytical
Language
eng
Abstract
Here the metabolism of 5-HT has been investigated in higher animals, the deuterostomes, which included the invertebrates Xenoturbella bocki, a marine worm, and Strongylocentrotus purppuratus, the sea urchin as well as mammals such as Rattus norvegicus. Studies were performed using a highly specialized capillary electrophoresis (CE) system designed to detect 5-HT and related compounds at attomole levels. The invertebrate deuterstomes investigated were found to metabolize 5-HT in a manner similar to both more primitive invertebrates and to vertebrates; results include the discovery of metabolites such as gammaglutamyl 5-HT, 5-HT sulfate (5-HT-SO4) and 5-hydroxyindole acetic acid (5-HIAA) in these organisms. A novel 5-HT metabolite in the rat (Rattus norvegicus ), 5-hydroxyindole thiazolidine carboxylic acid (5-HITCA), was characterized via mass spectrometry (MS) and further investigated using CE. Levels of 5-HT and some of its key metabolites were also investigated in this mammal under conditions of induced serotonin syndrome, a physiological condition caused by an excessive increase in 5-HT levels often associated with a combination of antidepressant therapies. This research contributes to our understanding of the metabolic pathways of 5-HT in both healthy and disease states. The findings aid in understanding the 5-HT link to various disorders.
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