Vancleef L, Van Den Broeck T, Thijs T, Steensels S, Briand L, Tack J, Depoortere I
Gut Peptide Research Lab, Translational Research Center for Gastrointestinal Disorders, Department of Clinical &Experimental Medicine, University of Leuven, Leuven, 3000, Belgium.
INRA UMR1324, CNRS UMR6265, Université de Bourgogne, Centre des Sciences du Goût et de l'Alimentation, F-21000, Dijon, France.
Sci Rep. 2015 Oct 29;5:15725. doi: 10.1038/srep15725.
Taste receptors on enteroendocrine cells sense nutrients and transmit signals that control gut hormone release. This study aimed to investigate the amino acid (AA) sensing mechanisms of the ghrelin cell in a gastric ghrelinoma cell line, tissue segments and mice. Peptone and specific classes of amino acids stimulate ghrelin secretion in the ghrelinoma cell line. Sensing of L-Phe occurs via the CaSR, monosodium glutamate via the TAS1R1-TAS1R3 while L-Ala and peptone act via 2 different amino acid taste receptors: CaSR &TAS1R1-TAS1R3 and CaSR &GPRC6A, respectively. The stimulatory effect of peptone on ghrelin release was mimicked ex vivo in gastric but not in jejunal tissue segments, where peptone inhibited ghrelin release. The latter effect could not be blocked by receptor antagonists for CCK, GLP-1 or somatostatin. In vivo, plasma ghrelin levels were reduced both upon intragastric (peptone or L-Phe) or intravenous (L-Phe) administration, indicating that AA- sensing is not polarized and is due to inhibition of ghrelin release from the stomach or duodenum respectively. In conclusion, functional AA taste receptors regulate AA-induced ghrelin release in vitro. The effects differ between stomach and jejunum but these local nutrient sensing mechanisms are overruled in vivo by indirect mechanisms inhibiting ghrelin release.
肠内分泌细胞上的味觉受体感知营养物质并传递控制肠道激素释放的信号。本研究旨在探究胃泌素瘤细胞系、组织片段和小鼠中胃饥饿素细胞的氨基酸（AA）传感机制。蛋白胨和特定种类的氨基酸可刺激胃泌素瘤细胞系中胃饥饿素的分泌。L-苯丙氨酸通过钙敏感受体（CaSR）感知，谷氨酸钠通过TAS1R1-TAS1R3感知，而L-丙氨酸和蛋白胨分别通过2种不同的氨基酸味觉受体起作用：CaSR和TAS1R1-TAS1R3以及CaSR和G蛋白偶联受体C6A（GPRC6A）。蛋白胨对胃饥饿素释放的刺激作用在离体胃组织片段中可被模拟，但在空肠组织片段中则不然，在空肠组织片段中蛋白胨会抑制胃饥饿素的释放。后一种作用不能被胆囊收缩素（CCK）、胰高血糖素样肽-1（GLP-1）或生长抑素的受体拮抗剂阻断。在体内，胃内给予（蛋白胨或L-苯丙氨酸）或静脉注射（L-苯丙氨酸）后，血浆胃饥饿素水平均降低，这表明氨基酸传感并非极化的，分别是由于胃或十二指肠中胃饥饿素释放受到抑制。总之，功能性氨基酸味觉受体在体外调节氨基酸诱导的胃饥饿素释放。胃和空肠的作用不同，但这些局部营养传感机制在体内被抑制胃饥饿素释放的间接机制所取代。
