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APPETITE, OBESITY, DIGESTION, AND METABOLISM

Role of CCK₁ and Y₂ receptors in activation of hindbrain neurons induced by intragastric administration of bitter taste receptor ligands

¹Department of Anatomy, Physiology, and Cell Biology, School of Veterinary Medicine, University of California, Davis; and ²CURE Digestive Diseases Research Center, Division of Digestive Diseases, Departments of Medicine and Neurobiology, David Geffen School of Medicine, University of California, Los Angeles, California

Submitted 19 September 2007 ; accepted in final form 7 November 2007

G-protein-coupled receptors signaling bitter taste (T2Rs) in the oral gustatory system and the -subunit of the taste-specific G-protein gustducin are expressed in the gastrointestinal (GI) tract. -Subunit of the taste-specific G-protein gustducin colocalizes with markers of enteroendocrine cells in human and mouse GI mucosa, including peptide YY. Activation of T2Rs increases cholecystokinin (CCK) release from the enteroendocrine cell line, STC-1. 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 CCK and peptide YY acting at CCK₁ and Y₂ receptors. Immunocytochemistry for the protooncogene c-Fos protein, a marker for neuronal activation, was used to determine activation of neurons in the midregion of the NTS, the region where vagal afferents from the GI tract terminate. Intragastric administration of the T2R agonist denatonium benzoate (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 had no effect on the response to 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.

bitter taste receptors; vagal afferent; nucleus of the solitary tract; Fos; cholecystokinin 1 receptor; Y₂ receptor

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				I. Kaji, S.-i. Karaki, Y. Fukami, M. Terasaki, and A. Kuwahara Secretory effects of a luminal bitter tastant and expressions of bitter taste receptors, T2Rs, in the human and rat large intestine Am J Physiol Gastrointest Liver Physiol, May 1, 2009; 296(5): G971 - G981. [Abstract] [Full Text] [PDF]

				S. Hao, M. Dulake, E. Espero, C. Sternini, H. E. Raybould, and L. Rinaman Central Fos expression and conditioned flavor avoidance in rats following intragastric administration of bitter taste receptor ligands Am J Physiol Regulatory Integrative Comp Physiol, March 1, 2009; 296(3): R528 - R536. [Abstract] [Full Text] [PDF]