Shin Yu-Kyong, Martin Bronwen, Golden Erin, Dotson Cedrick D, Maudsley Stuart, Kim Wook, Jang Hyeung-Jin, Mattson Mark P, Drucker Daniel J, Egan Josephine M, Munger Steven D
National Institute on Aging/NIH, Baltimore, Maryland 21224, USA.
J Neurochem. 2008 Jul;106(1):455-63. doi: 10.1111/j.1471-4159.2008.05397.x. Epub 2008 Jul 1.
In many sensory systems, stimulus sensitivity is dynamically modulated through mechanisms of peripheral adaptation, efferent input, or hormonal action. In this way, responses to sensory stimuli can be optimized in the context of both the environment and the physiological state of the animal. Although the gustatory system critically influences food preference, food intake and metabolic homeostasis, the mechanisms for modulating taste sensitivity are poorly understood. In this study, we report that glucagon-like peptide-1 (GLP-1) signaling in taste buds modulates taste sensitivity in behaving mice. We find that GLP-1 is produced in two distinct subsets of mammalian taste cells, while the GLP-1 receptor is expressed on adjacent intragemmal afferent nerve fibers. GLP-1 receptor knockout mice show dramatically reduced taste responses to sweeteners in behavioral assays, indicating that GLP-1 signaling normally acts to maintain or enhance sweet taste sensitivity. A modest increase in citric acid taste sensitivity in these knockout mice suggests GLP-1 signaling may modulate sour taste, as well. Together, these findings suggest a novel paracrine mechanism for the regulation of taste function.
在许多感觉系统中,刺激敏感性通过外周适应、传出输入或激素作用机制进行动态调节。通过这种方式,动物对感觉刺激的反应能够在环境和生理状态的背景下得到优化。尽管味觉系统对食物偏好、食物摄入和代谢稳态有着至关重要的影响,但调节味觉敏感性的机制仍知之甚少。在本研究中,我们报告称味蕾中的胰高血糖素样肽-1(GLP-1)信号传导可调节行为小鼠的味觉敏感性。我们发现GLP-1在哺乳动物味觉细胞的两个不同亚群中产生,而GLP-1受体则在相邻的味蕾内传入神经纤维上表达。GLP-1受体基因敲除小鼠在行为试验中对甜味剂的味觉反应显著降低,这表明GLP-1信号传导通常起到维持或增强甜味敏感性的作用。这些基因敲除小鼠对柠檬酸味觉敏感性的适度增加表明GLP-1信号传导也可能调节酸味。总之,这些发现提示了一种调节味觉功能的新型旁分泌机制。