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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August 2011
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Research Article|
July 27 2011
Gut bitter taste receptor signalling induces ABCB1 through a mechanism involving CCK
Tae-Il Jeon
;
Tae-Il Jeon
*Department of Molecular Biology and Biochemistry, University of California, Irvine, CA 92697, U.S.A.
†Metabolic Signaling and Disease Program, Sanford-Burnham Institute for Medical Research, Lake Nona, FL 32827, U.S.A.
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Young-Kyo Seo
;
Young-Kyo Seo
*Department of Molecular Biology and Biochemistry, University of California, Irvine, CA 92697, U.S.A.
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Timothy F. Osborne
Timothy F. Osborne
1
*Department of Molecular Biology and Biochemistry, University of California, Irvine, CA 92697, U.S.A.
†Metabolic Signaling and Disease Program, Sanford-Burnham Institute for Medical Research, Lake Nona, FL 32827, U.S.A.
1To whom correspondence should be addressed (email tosborne@sanfordburnham.org).
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Biochem J (2011) 438 (1): 33–37.
Article history
Received:
January 04 2011
Revision Received:
May 09 2011
Accepted:
May 19 2011
Accepted Manuscript online:
May 19 2011
Citation
Tae-Il Jeon, Young-Kyo Seo, Timothy F. Osborne; Gut bitter taste receptor signalling induces ABCB1 through a mechanism involving CCK. Biochem J 15 August 2011; 438 (1): 33–37. doi: https://doi.org/10.1042/BJ20110009
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