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Gut bitter taste receptor signalling induces ABCB1 through a mechanism involving CCK
Open accessAbstract
T2Rs (bitter taste-sensing type 2 receptors) are expressed in the oral cavity to prevent ingestion of dietary toxins through taste avoidance. They are also expressed in other cell types, including gut enteroendocrine cells, where their physiological role is enigmatic. Previously, we proposed that T2R-dependent CCK (cholecystokinin) secretion from enteroendocrine cells limits absorption of dietary toxins, but an active mechanism was lacking. In the present study we show that T2R signalling activates ABCB1 (ATP-binding cassette B1) in intestinal cells through a CCK signalling mechanism. PTC (phenylthiocarbamide), an agonist for the T2R38 bitter receptor, increased ABCB1 expression in both intestinal cells and mouse intestine. PTC induction of ABCB1 was decreased by either T2R38 siRNA (small interfering RNA) or treatment with YM022, a gastrin receptor antagonist. Thus gut ABCB1 is regulated through signalling by CCK/gastrin released in response to PTC stimulation of T2R38 on enteroendocrine cells. We also show that PTC increases the efflux activity of ABCB1, suggesting that T2R signalling limits the absorption of bitter tasting/toxic substances through modulation of gut efflux membrane transporters.
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Bitter taste receptors can be considered as potential targets to reduce hunger by stimulating the release of CCK.
“Bitter taste receptors can be considered as potential targets to reduce hunger by stimulating the release of CCK (61).”
From Vagus Nerve as Modulator of the Brain–Gut Axis in Psychiatric and Inflammatory Disorders (2018) · cites this paper as [61]
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Vagus Nerve as Modulator of the Brain–Gut Axis in Psychiatric and Inflammatory Disorders
Breit, S., Kupferberg, A., Rogler, G., & Hasler, G. (2018) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2018.00044 · Cited by 1,189
“Studies in rodents clearly indicate that leptin and CCK interact synergistically to induce short-term inhibition of food intake and long-term reduction of body weight (40).”
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Metadata
- Authors
- Jeon, T.-I., Seo, Y.-K., & Osborne, T. F.
- Affiliations
- Sanford Burnham Prebys Medical Discovery Institute (US)
- University of California, Irvine (US)
- Corresponding author
- Osborne, Timothy F.
- Venue
- Biochemical Journal
- Publisher
- Portland Press Ltd.
- Published
- 2011-07-27
- Volume
- 438
- Issue
- 1
- Pages
- 33-37
- ISSN
- 0264-6021 (ISSN-L)
- 1470-8728
- PMC
- PMC3319131
- OpenAlex
- W2066520363
- Cited by
- 127
- References
- 17
- Citations by year
- 2026: 7 · 2025: 8 · 2024: 5 · 2023: 4 · 2022: 6 · 2021: 11 · 2020: 12 · 2019: 8 · 2018: 12 · 2017: 11 · 2016: 10 · 2015: 10 · 2014: 8 · 2013: 9 · 2012: 3
- FWCI
- 6.80
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Biochemical Journal (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Heart, Lung, and Blood Institute (R01HL048044, HL48044)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK071021, DK71021)
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Biochemical Analysis and Sensing Techniques
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Keywords
- bitter taste receptors, P-glycoprotein, cholecystokinin, gastrin, enteroendocrine cells, phenylthiocarbamide, intestinal barrier
- MeSH terms
- Taste Receptors, Type 2, Animals, Cholecystokinin, Flow Cytometry, Gastrins, Hormones, Humans, Intestinal Mucosa, Intestines, Male, Phenylthiourea, Promoter Regions, Genetic, RNA, Messenger, Taste Buds, Blotting, Western, Signal Transduction, ATP Binding Cassette Transporter, Subfamily B, Caco-2 Cells, Enteroendocrine Cells, Reverse Transcriptase Polymerase Chain Reaction, ATP Binding Cassette Transporter, Subfamily B, Member 1, RNA, Small Interfering, Receptors, G-Protein-Coupled, Mice
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