Department of Molecular Biology and Biochemistry, University of California, Irvine, CA 92697, USA.
Biochem J. 2011 Aug 15;438(1):33-7. doi: 10.1042/BJ20110009.
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.
T2Rs（苦味感应型 2 型受体）在口腔中表达，以通过味觉回避防止摄入饮食毒素。它们也在其他细胞类型中表达，包括肠道内分泌细胞，其生理作用尚不清楚。先前，我们提出 T2R 依赖性 CCK（胆囊收缩素）从内分泌细胞分泌可限制饮食毒素的吸收，但缺乏主动机制。在本研究中，我们表明 T2R 信号通过 CCK 信号机制在肠道细胞中激活 ABCB1（ATP 结合盒 B1）。PTC（苯硫脲）是 T2R38 苦味受体的激动剂，可增加肠道细胞和小鼠肠道中 ABCB1 的表达。T2R38 siRNA（小干扰 RNA）或胃泌素受体拮抗剂 YM022 处理均可降低 PTC 诱导的 ABCB1。因此，通过 PTC 刺激内分泌细胞上的 T2R38 释放的 CCK/胃泌素信号调节肠道 ABCB1。我们还表明，PTC 增加了 ABCB1 的外排活性，表明 T2R 信号通过调节肠道外排膜转运体来限制苦味/有毒物质的吸收。
