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1 Department of Anatomy, Physiology and Cell Biology, School of Veterinary Medicine, University of California, Davis, California, United States; Anatomy, Physiology and Cell Biology, UC Davis School of Veteirnary Medicine, Davis, California, United States
2 Medicine, UCLA, Los Angeles, California, United States
3 Department of Anatomy, Physiology and Cell Biology, School of Veterinary Medicine, University of California, Davis, California, United States
* To whom correspondence should be addressed. E-mail: heraybould{at}ucdavis.edu.
G-protein coupled receptors signaling bitter taste (T2Rs) in the oral gustatory system and the 
subunit of the taste-specific G-protein gustducin (Ggust) are expressed in the gastrointestinal (GI) tract. Ggust co-localizes with markers of enteroendocrine cells including cholecystokinin (CCK) and peptide YY (PYY). The aim of this study was to determine whether T2R agonists in the GI tract activate neurons in the nucleus of the solitary tract (NTS) and whether this activation is mediated by CCK1 and Y2 receptors. Immunocytochemistry for the proto-oncogene c-fos protein was used to determine activation of neurons in the mid-region of the nucleus of the solitary tract (NTS). Intragastric administration of the T2R agonist denatonium (DB) or phenylthiocarbamide (PTC) or a combination of T2R agonists significantly increased the number of fos-positive neurons in the mid-NTS; subdiaphragmatic vagotomy abolished the NTS response to the mixture of T2R agonists. Deletion of CCK1 receptor gene or blockade of CCK1 receptors with devazepide abolishes the activation of NTS neurons in response to DB, but not PTC. Administration of the Y2 receptor antagonist BIIE0246 blocks the activation of NTS neurons to DB, but not PTC. These findings suggest that activation of neurons in the NTS following administration of T2R agonists to the GI tract involves CCK1 and Y2 receptors located on vagal afferent terminals in the gut wall. T2Rs may regulate GI function via release of regulatory peptides and activation of the vagal reflex pathway.
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