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Serotonin Is an Endogenous Regulator...

Manzella, Christopher.

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Serotonin Is an Endogenous Regulator of the Aryl Hydrocarbon Receptor in the Intestine.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Serotonin Is an Endogenous Regulator of the Aryl Hydrocarbon Receptor in the Intestine./
Author:	Manzella, Christopher.
Published:	Ann Arbor : ProQuest Dissertations & Theses, : 2021,
Description:	220 p.
Notes:	Source: Dissertations Abstracts International, Volume: 83-02, Section: B.
Contained By:	Dissertations Abstracts International83-02B.
Subject:	Cellular biology. -
Online resource:	https://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=28722838
ISBN:	9798534687101

Serotonin Is an Endogenous Regulator of the Aryl Hydrocarbon Receptor in the Intestine.
Manzella, Christopher.

Serotonin Is an Endogenous Regulator of the Aryl Hydrocarbon Receptor in the Intestine. - Ann Arbor : ProQuest Dissertations & Theses, 2021 - 220 p.

Source: Dissertations Abstracts International, Volume: 83-02, Section: B.

Thesis (Ph.D.)--University of Illinois at Chicago, 2021.

This item must not be sold to any third party vendors.

Serotonin (5-hydroxytryptamine, 5-HT) is a tryptophan-derived neurotransmitter and hormone that plays an important role in regulating diverse physiological processes in both the brain and the gut. In the GI tract, 5-HT modulates electrolyte secretion and absorption, blood flow, perception of nausea or pain, and intestinal motility. The GI tract is a major source of 5-HT, with 95% of the whole body 5-HT being synthesized by specialized epithelial cells called enterochromaffin (EC) cells. EC cells release 5-HT into the intestinal lumen and the lamina propria where it can bind to 5-HT receptors (5-HTRs) to elicit its various physiological actions. Extracellular 5-HT is internalized by the serotonin transporter (SLC6A4, SERT), which transports 5-HT into the cell with high affinity.Decreased SERT expression and altered extracellular 5-HT levels have been implicated in several GI disorders such as Crohn's disease (CD), ulcerative colitis (UC) and irritable bowel syndrome (IBS). With an overall goal to understand the impact of SERT deficiency on intestinal physiology, we performed a microarray analysis to compare gene expression in the ileal mucosa between wild-type (WT) mice and SERT knockout (KO) mice. Interestingly, the most down-regulated gene in the SERT KO mice was cytochrome P450 family 1, member A1 (Cyp1a1) which is the primary gene target of the aryl hydrocarbon receptor (AhR) signaling pathway.Aryl hydrocarbon receptor (AhR) is a ligand-activated nuclear receptor that plays critical roles in immune regulation and detoxification of environmental contaminants such as polycyclic aromatic hydrocarbons (PAHs). Over recent years, a new role for AhR has been established in the recognition of bacterial products and modulation of microbial pathogen defenses. While tryptophan metabolites have been shown to activate AhR, the involvement of 5-HT and serotonergic machinery in AhR signaling has not been previously established. Thus, the purpose of this study was to investigate the link between the AhR and serotonergic pathways to establish a new role of intestinal 5-HT. Learning more about this link will enhance our understanding of how 5-HT contributes to intestinal homeostasis under basal conditions, while also providing a novel perspective of how 5-HT can play a role in the pathophysiology of intestinal disorders.

ISBN: 9798534687101Subjects--Topical Terms:

3172791
Cellular biology.
Subjects--Index Terms:

Serotonin

Serotonin Is an Endogenous Regulator of the Aryl Hydrocarbon Receptor in the Intestine.
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300 $a 220 p.
500 $a Source: Dissertations Abstracts International, Volume: 83-02, Section: B.
500 $a Advisor: Rao, Mrinalini C.;Gill, Ravinder K.
502 $a Thesis (Ph.D.)--University of Illinois at Chicago, 2021.
506 $a This item must not be sold to any third party vendors.
520 $a Serotonin (5-hydroxytryptamine, 5-HT) is a tryptophan-derived neurotransmitter and hormone that plays an important role in regulating diverse physiological processes in both the brain and the gut. In the GI tract, 5-HT modulates electrolyte secretion and absorption, blood flow, perception of nausea or pain, and intestinal motility. The GI tract is a major source of 5-HT, with 95% of the whole body 5-HT being synthesized by specialized epithelial cells called enterochromaffin (EC) cells. EC cells release 5-HT into the intestinal lumen and the lamina propria where it can bind to 5-HT receptors (5-HTRs) to elicit its various physiological actions. Extracellular 5-HT is internalized by the serotonin transporter (SLC6A4, SERT), which transports 5-HT into the cell with high affinity.Decreased SERT expression and altered extracellular 5-HT levels have been implicated in several GI disorders such as Crohn's disease (CD), ulcerative colitis (UC) and irritable bowel syndrome (IBS). With an overall goal to understand the impact of SERT deficiency on intestinal physiology, we performed a microarray analysis to compare gene expression in the ileal mucosa between wild-type (WT) mice and SERT knockout (KO) mice. Interestingly, the most down-regulated gene in the SERT KO mice was cytochrome P450 family 1, member A1 (Cyp1a1) which is the primary gene target of the aryl hydrocarbon receptor (AhR) signaling pathway.Aryl hydrocarbon receptor (AhR) is a ligand-activated nuclear receptor that plays critical roles in immune regulation and detoxification of environmental contaminants such as polycyclic aromatic hydrocarbons (PAHs). Over recent years, a new role for AhR has been established in the recognition of bacterial products and modulation of microbial pathogen defenses. While tryptophan metabolites have been shown to activate AhR, the involvement of 5-HT and serotonergic machinery in AhR signaling has not been previously established. Thus, the purpose of this study was to investigate the link between the AhR and serotonergic pathways to establish a new role of intestinal 5-HT. Learning more about this link will enhance our understanding of how 5-HT contributes to intestinal homeostasis under basal conditions, while also providing a novel perspective of how 5-HT can play a role in the pathophysiology of intestinal disorders.
590 $a School code: 0799.
650 4 $a Cellular biology. $3 3172791
650 4 $a Molecular biology. $3 517296
650 4 $a Physiology. $3 518431
650 4 $a Inflammatory bowel disease. $3 3560376
650 4 $a Tumor necrosis factor-TNF. $3 3560383
650 4 $a Epidermal growth factor. $3 2107074
650 4 $a Kinases. $3 3558077
650 4 $a Irritable bowel syndrome. $3 3560384
653 $a Serotonin
653 $a Intestine
653 $a Inflammatory bowel disease
653 $a Aryl hydrocarbon receptor
653 $a Xenobiotic metabolism
653 $a Serotonin transporter
653 $a Cytochrome P450
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690 $a 0307
690 $a 0719
710 2 $a University of Illinois at Chicago. $b Physiology and Biophysics. $3 3560382
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792 $a 2021
793 $a English
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