NDLI: Luminal regulation of normal and neoplastic human EC cell serotonin release is mediated by bile salts, amines, tastants, and olfactants.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Kidd, Mark Modlin, Irvin M. Gustafsson, Bjorn I. Drozdov, Ignat Hauso, Oyvind Pfragner, Roswitha
Description	Country affiliation: United States Author Affiliation: Kidd M ( 1Gastrointestinal Pathobiology Research Group, Yale University School of Medicine, New Haven, Connecticut 06520, USA.)
Abstract	Mechanisms by which gut luminal content regulates secretion and motility are ill understood. We evaluated whether neuroendocrine enterochromaffin (EC) cells act as luminal sensors for a wide variety of nutrients and defined the secretory mechanisms of this process. Pure (98-99%) FACS-sorted human EC cells and neoplastic EC cells (KRJ-I) were studied. RT-PCR identified transcripts for T2R1 (bitter), OR1G1 (class II olfactory) and trace amine (TAR1) G protein-coupled receptors (GPCRs) and transporters for glutamine (SNAT1/2), glucose (GLUT1/3/SGLT1), and bile salts (ABST). Glutamine and sodium deoxycholate stimulated 5-HT release (EC(50) = 0.002-0.2 microM; 2-fold release) but were 10-100 times more potent in neoplastic EC cells, which also secreted 6-13 times more 5-HT. Tastants (caffeine, tyramine, octopamine) and olfactants (thymol and eugenol) also stimulated normal and neoplastic EC cell 5-HT secretion (EC(50) = 1.2 nM to 2.1 microM and 0.05 nM to 0.1 microM release, respectively); 2-deoxyglucose and the artificial sweetener sucralose also stimulated (EC(50) = 9.2 and 0.38 nM). 5-HT release was associated with ERK phosphorylation (1.5-fold, P < 0.02) and could be inhibited by a somatostatin analog (IC(50) = 1 pM). Eleven secretory associated genes including the vesicle docking inhibitor STXBP3 were upregulated in response to glutamine and bile salt stimulation in neoplastic EC cells. Targeting STXBP3 expression by use of antisense knockdown significantly (P < 0.05) reduced 5-HT secretion. In conclusion, EC cells express GPCRs and transporters for luminal tastants, olfactants, glutamine, glucose, and bile salts. Activation includes a panel of secretory genes, ERK phosphorylation, and 5-HT secretion. Luminal EC cell regulation is likely to be as important as G cell regulation in gastric acid secretion; development of agents to target EC cell function is therefore a critical therapeutic goal.
File Format	HTM / HTML
ISSN	01931857
Issue Number	2
Volume Number	295
e-ISSN	15221547
Journal	AJP: Gastrointestinal and Liver Physiology
Language	English
Publisher	American Physiological Society
Publisher Date	2008-08-01
Publisher Place	United States
Access Restriction	Subscribed
Subject Keyword	Discipline Physiology Discipline Gastroenterology Bile Acids And Salts Physiology Carcinoid Tumor Secretion Enterochromaffin Cells Intestinal Neoplasms Serotonin Amino Acid Transport System A Caffeine Pharmacology Genetics Cell Line, Tumor Deoxycholic Acid Deoxyglucose Drug Effects Extracellular Signal-regulated Map Kinases Glucose Transport Proteins, Facilitative Glutamine Humans Intestine, Small Organic Anion Transporters, Sodium-dependent Receptors, G-protein-coupled Receptors, Metabotropic Glutamate Receptors, Odorant Sodium-glucose Transporter 1 Somatostatin Sucrose Analogs & Derivatives Symporters Tyrosine Journal Article Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Hepatology Physiology Physiology (medical) Gastroenterology

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