Gut bitter taste receptor signalling induces ABCB1 through a mechanism involving CCK

Tae Il Jeon, Young Kyo Seo, Timothy Osborne

Research output: Contribution to journalArticle

Abstract

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 activemechanismwas lacking. In the present study we showthat T2R signalling activates ABCB1 (ATP-binding cassette B1) in intestinal cells through a CCK signallingmechanism. 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.

Original languageEnglish (US)
Pages (from-to)33-37
Number of pages5
JournalBiochemical Journal
Volume438
Issue number1
DOIs
Publication statusPublished - Aug 15 2011
Externally publishedYes

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Keywords

  • ATP-binding cassette B1 (ABCB1) efflux transporter
  • Bitter taste-sensing type 2 receptor (T2R)
  • Cholecystokinin (CCK)
  • Enteroendocrine cell
  • Gut efflux membrane transporter

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

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