Hochheimer Andreas, Krohn Michael, Rudert Kerstin, Riedel Katja, Becker Sven, Thirion Christian, Zinke Holger
BRAIN AG, Darmstaedter Str. 34-36, 64673 Zwingenberg, Germany.
Chem Senses. 2014 May;39(4):359-77. doi: 10.1093/chemse/bju009. Epub 2014 Mar 12.
Investigating molecular mechanisms underlying human taste sensation requires functionally dedicated and at the same time proliferating human taste cells. Here, we isolated viable human fungiform taste papillae cells from biopsy samples, adenovirally transduced proliferation promoting genes, and obtained stably proliferating cell lines. Analysis of gene expression of 1 human taste cell line termed HTC-8 revealed that these cells express 13 TAS2R bitter taste receptor genes, CD36, OXTR encoding oxytocin receptor, as well as genes implicated with signal transduction and cell fate control. Bitter tastants triggered functionally distinct signaling pathways in HTC-8 cells. Salicin elicited phospholipase C-dependent calcium signaling and no cell depolarization. In contrast, stimulation with saccharin, aristolochic acid, or phenylthiocarbamide triggered cell depolarization and phospholipase C-independent calcium influx. Simultaneous stimulation with salicin and saccharin revealed that saccharin can enhance the phospholipase C-dependent response to salicin indicating crosstalk of signaling pathways. Our results show that HTC-8 cells are programmed to bitter taste reception but are also responsive to fatty acids, oxytocin, and somatosensory stimuli, whereas HTC-8 cells are insensitive to compounds representing other basic taste qualities.
研究人类味觉背后的分子机制需要功能专一且同时能增殖的人类味觉细胞。在此，我们从活检样本中分离出有活力的人类菌状乳头味觉细胞，通过腺病毒转导增殖促进基因，获得了稳定增殖的细胞系。对一个名为HTC - 8的人类味觉细胞系的基因表达分析表明，这些细胞表达13个TAS2R苦味受体基因、CD36、编码催产素受体的OXTR，以及与信号转导和细胞命运控制相关的基因。苦味剂在HTC - 8细胞中触发功能不同的信号通路。水杨苷引发磷脂酶C依赖性钙信号，且无细胞去极化。相反，用糖精、马兜铃酸或苯硫脲刺激会触发细胞去极化和非磷脂酶C依赖性钙内流。同时用水杨苷和糖精刺激表明，糖精可增强对水杨苷的磷脂酶C依赖性反应，表明信号通路存在串扰。我们的结果表明，HTC - 8细胞被设定为对苦味有反应，但也对脂肪酸、催产素和体感刺激有反应，而HTC - 8细胞对代表其他基本味觉特性的化合物不敏感。
