The Role of ATP and Purinergic Receptors in Taste Signaling.
The Role of ATP and Purinergic Receptors in Taste Signaling.
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DOI：
10.1007/164_2021_518
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发表时间：
2022
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这篇综述总结了我们对味觉中 ATP 信号传导的理解，并描述了新的研究方向。 ATP 满足被视为神经递质的所有必要标准：(1) 存在于味觉细胞中，与所有细胞一样； (2)适当的味觉刺激后释放； (3) 与味觉传入神经元上的同源嘌呤能受体 P2X2 和 P2X3 结合，以及 (4) 释放后，通过味蕾中 I 型神经胶质样细胞上表达的外核苷酸酶 NTPDase2 酶促降解为腺苷和其他核苷酸。重要的是，P2X2 和 P2X3 的双敲除或 P2X3 的药理抑制消除了所有味道品质的传递。在 II 型味觉细胞（对甜味、苦味或鲜味刺激做出反应的味觉细胞）中，ATP 通过由 CALHM1 和 CALHM3 组成的大电导离子通道以非囊泡形式释放，这些离子通道在与传入味觉神经纤维接触的区域形成所谓的通道突触。虽然仅在 II 型细胞中检测到 ATP 释放，但咸味和酸味刺激的传递也需要 ATP 释放，而咸味和酸味刺激主要由 III 型味觉细胞介导。 III 型细胞向传入纤维发出信号所需的 ATP 来源仍不清楚，这是未来实验的重点。离子型嘌呤能受体 P2X3 在许多感觉传入神经上广泛表达，并且已成为治疗慢性咳嗽和疼痛的治疗靶点。然而，它对味觉信号传导的要求使得治疗工作变得复杂，因为接受 P2X3 拮抗剂的患者报告出现严重的味觉障碍并且变得不依从。
This review summarizes our understanding of ATP signaling in taste and describes new directions for research. ATP meets all requisite criteria to be considered a neurotransmitter: (1) presence in taste cells, as in all cells; (2) release upon appropriate taste stimulation; (3) binding to cognate purinergic receptors P2X2 and P2X3 on gustatory afferent neurons, and (4) after release, enzymatic degradation to adenosine and other nucleotides by the ectonucleotidase, NTPDase2, expressed on the Type I, glial-like cells in the taste bud. Importantly, double knockout of P2X2 and P2X3 or pharmacological inhibition of P2X3 abolishes transmission of all taste qualities. In Type II taste cells (those that respond to sweet, bitter, or umami stimuli), ATP is released non-vesicularly by a large conductance ion channel composed of CALHM1 and CALHM3, which form a so-called channel synapse at areas of contact with afferent taste nerve fibers. Although ATP release has been detected only from Type II cells, it is also required for the transmission of salty and sour stimuli, which are mediated primarily by the Type III taste cells. The source of the ATP required for Type III cell signaling to afferent fibers is still unclear and is a focus for future experiments. The ionotropic purinergic receptor, P2X3, is widely expressed on many sensory afferents and has been a therapeutic target for treating chronic cough and pain. However, its requirement for taste signaling has complicated efforts at treatment since patients given P2X3 antagonists report substantial disturbances of taste and become non-compliant.