title: Activation of the umami taste receptor (T1R1/T1R3) initiates the peristaltic reflex and pellet propulsion in the distal colon.
abstract: Intraluminal nutrients in the gut affect the peristaltic reflex, although the mechanism is not well defined. Recent evidence supports the presence of taste receptors and their signaling components in enteroendocrine cells, although their function is unclear. This study aimed to determine if nutrients modify colonic motility through activation of taste receptors. Colonic sections were immunostained for the umami taste receptor T1R1/T1R3, which mediates the response to umami ligands, such as monosodium glutamate (MSG), in taste cells. Ascending contraction, descending relaxation, and calcitonin gene-related peptide release were measured in three-chamber flat-sheet preparations of rat colon in response to MSG alone or with inosine 5'-monophosphate (IMP). Velocity of artificial fecal pellet propulsion was measured by video recording in guinea pig distal colon. T1R1/T1R3 receptors were present in enteroendocrine cells of colonic sections from human, rat, mouse, and guinea pig. MSG initiated ascending contraction and descending relaxation components of the peristaltic reflex and calcitonin gene-related peptide release in flat-sheet preparations. IMP augmented the MSG-induced effects, suggesting activation of T1R1/T1R3 receptors. In T1R1(-/-) mice, mucosal stroking, but not MSG, elicited a peristaltic reflex. Intraluminal perfusion of MSG enhanced the velocity of artificial fecal pellet propulsion, which was also augmented by IMP. Propulsion was also increased by l-cysteine, but not l-tryptophan, supporting a role of T1R1/T1R3 receptors. We conclude that T1R1/T1R3 activation by luminal MSG or l-cysteine elicits a peristaltic reflex and CGRP release and increases the velocity of pellet propulsion in distal colon. This mechanism may explain how nutrients regulate colonic propulsion.
authors.affiliation: Department of Physiology and Biophysics, Virginia Commonwealth University School of Medicine, Richmond, Virginia; and.
authors.forename: Derek M
authors.initials: DM
authors.lastname: Kendig
authors.affiliation: Department of Physiology and Biophysics, Virginia Commonwealth University School of Medicine, Richmond, Virginia; and.
authors.forename: Norman R
authors.initials: NR
authors.lastname: Hurst
authors.affiliation: Department of Physiology and Biophysics, Virginia Commonwealth University School of Medicine, Richmond, Virginia; and.
authors.forename: Zachary L
authors.initials: ZL
authors.lastname: Bradley
authors.affiliation: Department of Physiology and Biophysics, Virginia Commonwealth University School of Medicine, Richmond, Virginia; and.
authors.forename: Sunila
authors.initials: S
authors.lastname: Mahavadi
authors.affiliation: Department of Physiology and Biophysics, Virginia Commonwealth University School of Medicine, Richmond, Virginia; and Department of Medicine, VCU Program in Enteric Neuromuscular Sciences, Virginia Commonwealth University School of Medicine, Richmond, Virginia.
authors.forename: John F
authors.initials: JF
authors.lastname: Kuemmerle
authors.affiliation: Department of Physiology and Biophysics, Virginia Commonwealth University School of Medicine, Richmond, Virginia; and.
authors.forename: Vijay
authors.initials: V
authors.lastname: Lyall
authors.affiliation: Department of Physiology and Biophysics, Virginia Commonwealth University School of Medicine, Richmond, Virginia; and.
authors.forename: John
authors.initials: J
authors.lastname: DeSimone
authors.affiliation: Department of Physiology and Biophysics, Virginia Commonwealth University School of Medicine, Richmond, Virginia; and Department of Medicine, VCU Program in Enteric Neuromuscular Sciences, Virginia Commonwealth University School of Medicine, Richmond, Virginia.
authors.forename: Karnam S
authors.initials: KS
authors.lastname: Murthy
authors.affiliation: Department of Physiology and Biophysics, Virginia Commonwealth University School of Medicine, Richmond, Virginia; and Department of Medicine, VCU Program in Enteric Neuromuscular Sciences, Virginia Commonwealth University School of Medicine, Richmond, Virginia jgrider@vcu.edu.
authors.forename: John R
authors.initials: JR
authors.lastname: Grider
mesh_terms: D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D003106:Colon / Q000187:drug effects*; D003545:Cysteine / Q000494:pharmacology; D005260:Female; D005503:Food Additives; D005769:Gastrointestinal Motility / Q000187:drug effects*; D006168:Guinea Pigs; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010528:Peristalsis / Q000187:drug effects*; D017207:Rats, Sprague-Dawley; D043562:Receptors, G-Protein-Coupled / Q000187:drug effects*; D012970:Sodium Glutamate / Q000494:pharmacology; D013649:Taste / Q000187:drug effects*; D014364:Tryptophan / Q000494:pharmacology
chemical_list: D005503:Food Additives; D043562:Receptors, G-Protein-Coupled; C431926:taste receptors, type 1; D014364:Tryptophan; D015740:Calcitonin Gene-Related Peptide; D003545:Cysteine; D012970:Sodium Glutamate
keywords: chemosensation; human colon; monosodium glutamate, T1R1/T1R3; motility