Luminal chemosensing in the duodenal mucosa

Akiba, Yasutada; Kaunitz, Jonathan D.

doi:10.1111/j.1748-1716.2010.02149.x

Cited by 25 publications

(11 citation statements)

References 70 publications

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“…In addition, mGluR receptors are found in the gut (16,194). Thus, as reviewed elsewhere (15,26,113), all the major amino acidsensing elements of the oral cavity are present in more distal areas of the gastrointestinal tract. It is possible that, like current conjectures about multiple umami taste receptors in the mouth, the presence of glutamate and other amino acids in the gut may be detected in multiple locations with different receptors.…”

Section: Oral and Postoral Protein Sensing And Preferencementioning

confidence: 97%

Role of gut nutrient sensing in stimulating appetite and conditioning food preferences

Sclafani

Ackroff

2012

American Journal of Physiology-Regulatory, Integrative and Comp

167

186

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The discovery of taste and nutrient receptors (chemosensors) in the gut has led to intensive research on their functions. Whereas oral sugar, fat, and umami taste receptors stimulate nutrient appetite, these and other chemosensors in the gut have been linked to digestive, metabolic, and satiating effects that influence nutrient utilization and inhibit appetite. Gut chemosensors may have an additional function as well: to provide positive feedback signals that condition food preferences and stimulate appetite. The postoral stimulatory actions of nutrients are documented by flavor preference conditioning and appetite stimulation produced by gastric and intestinal infusions of carbohydrate, fat, and protein. Recent findings suggest an upper intestinal site of action, although postabsorptive nutrient actions may contribute to flavor preference learning. The gut chemosensors that generate nutrient conditioning signals remain to be identified; some have been excluded, including sweet (T1R3) and fatty acid (CD36) sensors. The gut-brain signaling pathways (neural, hormonal) are incompletely understood, although vagal afferents are implicated in glutamate conditioning but not carbohydrate or fat conditioning. Brain dopamine reward systems are involved in postoral carbohydrate and fat conditioning but less is known about the reward systems mediating protein/glutamate conditioning. Continued research on the postoral stimulatory actions of nutrients may enhance our understanding of human food preference learning.

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Section: Oral and Postoral Protein Sensing And Preferencementioning

confidence: 97%

Role of gut nutrient sensing in stimulating appetite and conditioning food preferences

Sclafani

Ackroff

2012

American Journal of Physiology-Regulatory, Integrative and Comp

167

186

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“…Akiba and colleagues reported the presence of T1R1/T1R3 in the duodenum as coperfusion of amino acids L-aspartate, L-leucine, and L-alanine with IMP increasing HCO 3 − secretion; this reaction echoes that of L-glutamate and IMP [30, 52]. Further developments in this subject are hindered by the lack of specific antibodies and selective agonists and antagonists for these receptors in the GI tract [53]. Future studies may uncover mechanisms for sensing all twenty L-amino acids.…”

Section: G Protein-coupled Receptors and Ligand Preferencesmentioning

confidence: 99%

Recent Advances in Gut Nutrient Chemosensing

Nguyen¹,

Akiba²,

Kaunitz³

2012

CMC

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The field of gut nutrient chemosensing is evolving rapidly. Recent advances have uncovered the mechanism by which specific nutrient components evoke multiple metabolic responses. Deorphanization of G protein-coupled receptors (GPCRs) in the gut has helped identify previously unliganded receptors and their cognate ligands. In this review, we discuss nutrient receptors, their ligand preferences, and the evoked neurohormonal responses. Family A GPCRs includes receptor GPR93, which senses protein and proteolytic degradation products, and free fatty acid-sensing receptors. Short-chain free fatty acids are ligands for FFA2, previously GPR43, and FFA3, previously GPR41. FFA1, previously GPR40, is activated by long-chain fatty acids with GPR120 activated by medium- and long-chain fatty acids. The GPR119 agonist ethanolamide oleoylethanolamide (OEA) and bile acid GPR131 agonists have also been identified. Family C receptors ligand preferences include L-amino acids, carbohydrate, and tastants. The metabotropic glutamate receptor (mGluR), calcium-sensing receptor (CaR), and GPCR family C, group 6, subtype A receptor (GPRC6A) mediate L-amino acid-sensing. Taste receptors have a proposed role in intestinal chemosensing; sweet, bitter, and umami evoke responses in the gut via GPCRs. The mechanism of carbohydrate-sensing remains controversial: the heterodimeric taste receptor T1R2/T1R3 and sodium glucose cotransporter 1 (SGLT-1) expressed in L cells are the two leading candidates. Identification of specific nutrient receptors and their respective ligands can provide novel therapeutic targets for the treatment of diabetes, acid reflux, foregut mucosal injury, and obesity.

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“…Indeed, luminal L -Glu stimulates gastric vagal afferents through the release of nitric oxide and 5-hydroxytryptamine [46]. Our study suggests that luminal L -Glu enhances mucosal defense mechanisms via multiple L -Glu receptors in the duodenum [47]. …”

Section: Luminal Amino Acid Sensing and Mucosal Defensesmentioning

confidence: 99%

Duodenal Chemosensing and Mucosal Defenses

Akiba

Kaunitz²

2011

Digestion

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The duodenal mucosa is exposed to endogenous and exogenous chemicals, including acid, CO₂, bile acids and nutrients. Mucosal chemical sensors are necessary to exert physiological responses such as secretion, digestion, absorption, and motility. We propose a mucosal chemosensing system by which luminal chemicals are sensed via mucosal acid sensors and G-protein-coupled receptors. Luminal acid/CO₂ sensing consists of ecto- and cytosolic carbonic anhydrases, epithelial ion transporters, and acid sensors expressed on the afferent nerves in the duodenum. Furthermore, a luminal L-glutamate signal is mediated via mucosal L-glutamate receptors, including metabotropic glutamate receptors and taste receptor 1 family heterodimers, with activation of afferent nerves and cyclooxygenase, whereas luminal Ca²⁺ is differently sensed via the calcium-sensing receptor in the duodenum. Recent studies also show the involvement of enteroendocrine G-protein-coupled receptors in bile acid and fatty acid sensing in the duodenum. These luminal chemosensors help activate mucosal defense mechanisms in or- der to maintain the mucosal integrity and physiological responses. Stimulation of luminal chemosensing in the duodenal mucosa may prevent mucosal injury, affect nutrient metabolism, and modulate sensory nerve activity.

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Luminal chemosensing in the duodenal mucosa

Cited by 25 publications

References 70 publications

Role of gut nutrient sensing in stimulating appetite and conditioning food preferences

Role of gut nutrient sensing in stimulating appetite and conditioning food preferences

Recent Advances in Gut Nutrient Chemosensing

Duodenal Chemosensing and Mucosal Defenses

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