Mace Oliver J, Lister Norma, Morgan Emma, Shepherd Emma, Affleck Julie, Helliwell Philip, Bronk John R, Kellett George L, Meredith David, Boyd Richard, Pieri Myrtani, Bailey Pat D, Pettcrew Rachel, Foley David
Department of Biology (Area 3), The University of York, Heslington, York YO10 5YW, UK.
J Physiol. 2009 Jan 15;587(1):195-210. doi: 10.1113/jphysiol.2008.159616. Epub 2008 Nov 10.
T1R taste receptors are present throughout the gastrointestinal tract. Glucose absorption comprises active absorption via SGLT1 and facilitated absorption via GLUT2 in the apical membrane. Trafficking of apical GLUT2 is rapidly up-regulated by glucose and artificial sweeteners, which act through T1R2 + T1R3/alpha-gustducin to activate PLC beta2 and PKC betaII. We therefore investigated whether non-sugar nutrients are regulated by taste receptors using perfused rat jejunum in vivo. Under different conditions, we observed a Ca(2+)-dependent reciprocal relationship between the H(+)/oligopeptide transporter PepT1 and apical GLUT2, reflecting the fact that trafficking of PepT1 and GLUT2 to the apical membrane is inhibited and activated by PKC betaII, respectively. Addition of L-glutamate or sucralose to a perfusate containing low glucose (20 mM) each activated PKC betaII and decreased apical PepT1 levels and absorption of the hydrolysis-resistant dipeptide L-Phe(PsiS)-L-Ala (1 mM), while increasing apical GLUT2 and glucose absorption within minutes. Switching perfusion from mannitol to glucose (75 mM) exerted similar effects. c-glutamate induced rapid GPCR internalization of T1R1, T1R3 and transducin, whereas sucralose internalized T1R2, T1R3 and alpha-gustducin. We conclude that L-glutamate acts via amino acid and glucose via sweet taste receptors to coordinate regulation of PepT1 and apical GLUT2 reciprocally through a common enterocytic pool of PKC betaII. These data suggest the existence of a wider Ca(2+) and taste receptor-coordinated transport network incorporating other nutrients and/or other stimuli capable of activating PKC betaII and additional transporters, such as the aspartate/glutamate transporter, EAAC1, whose level was doubled by L-glutamate. The network may control energy supply.
T1R味觉受体存在于整个胃肠道中。葡萄糖吸收包括通过SGLT1的主动吸收和通过顶端膜上的GLUT2的易化吸收。顶端GLUT2的转运通过葡萄糖和人工甜味剂迅速上调，它们通过T1R2 + T1R3/α-味导素作用以激活PLCβ2和PKCβII。因此，我们使用体内灌注的大鼠空肠研究了非糖营养物质是否受味觉受体调节。在不同条件下，我们观察到H(+)/寡肽转运体PepT1与顶端GLUT2之间存在Ca(2+)依赖性的相互关系，这反映了PepT1和GLUT2向顶端膜的转运分别被PKCβII抑制和激活这一事实。向含有低葡萄糖（20 mM）的灌注液中添加L-谷氨酸或三氯蔗糖均可激活PKCβII，并降低顶端PepT1水平以及抗水解二肽L-Phe(PsiS)-L-Ala（1 mM）的吸收，同时在数分钟内增加顶端GLUT2和葡萄糖吸收。将灌注液从甘露醇切换为葡萄糖（75 mM）也产生了类似的效果。L-谷氨酸诱导T1R1、T1R3和转导素的GPCR快速内化，而三氯蔗糖使T1R2、T1R3和α-味导素内化。我们得出结论，L-谷氨酸通过氨基酸起作用，葡萄糖通过甜味受体起作用，通过共同的肠细胞PKCβII池相互协调调节PepT1和顶端GLUT2。这些数据表明存在一个更广泛的Ca(2+)和味觉受体协调的转运网络，该网络包含其他营养物质和/或其他能够激活PKCβII和其他转运体的刺激物，例如天冬氨酸/谷氨酸转运体EAAC1，其水平被L-谷氨酸加倍。该网络可能控制能量供应。
