Huang Anthony Y, Wu Sandy Y
Department of Anatomy, Southern Illinois University School of Medicine, Carbondale, IL, USA.
Center for Integrated Research in Cognitive and Neural Science, Southern Illinois University School of Medicine, Carbondale, IL, USA.
Br J Pharmacol. 2018 Apr;175(7):1039-1053. doi: 10.1111/bph.14142. Epub 2018 Feb 23.
Capsaicin-mediated modulation of taste nerve responses is thought to be produced indirectly by the actions of neuropeptides, for example, CGRP and substance P (SP), on taste cells implying they play a role in taste sensitivity. During the processing of gustatory information in taste buds, CGRP shapes peripheral taste signals via serotonergic signalling. The underlying assumption has been that SP exerts its effects on taste transmitter secretion in taste buds of mice.
To test this assumption, we investigated the net effect of SP on taste-evoked ATP secretion from mouse taste buds, using functional calcium imaging with CHO cells expressing high-affinity transmitter receptors as cellular biosensors.
Our results showed that SP elicited PLC activation-dependent intracellular Ca transients in taste cells via neurokinin 1 receptors, most likely on glutamate-aspartate transporter-expressing Type I cells. Furthermore, SP caused Type I cells to secrete GABA.
Combined with the recent findings that GABA depresses taste-evoked ATP secretion, the current results indicate that SP elicited secretion of GABA, which provided negative feedback onto Type II (receptor) cells to reduce taste-evoked ATP secretion. These findings are consistent with a role for SP as an inhibitory transmitter that shapes the peripheral taste signals, via GABAergic signalling, during the processing of gustatory information in taste buds. Notably, the results suggest that SP is intimately associated with GABA in mammalian taste signal processing and demonstrate an unanticipated route for sensory information flow within the taste bud.
辣椒素介导的味觉神经反应调节被认为是由神经肽（如降钙素基因相关肽（CGRP）和P物质（SP））对味觉细胞的作用间接产生的，这意味着它们在味觉敏感性中发挥作用。在味蕾中味觉信息的处理过程中，CGRP通过5-羟色胺能信号传导塑造外周味觉信号。一直以来的假设是，SP对小鼠味蕾中的味觉递质分泌发挥作用。
为了验证这一假设，我们使用表达高亲和力递质受体的CHO细胞作为细胞生物传感器进行功能性钙成像，研究了SP对小鼠味蕾味觉诱发的ATP分泌的净效应。
我们的结果表明，SP通过神经激肽1受体在味觉细胞中引发PLC激活依赖性细胞内钙瞬变，最有可能作用于表达谷氨酸-天冬氨酸转运体的I型细胞。此外，SP导致I型细胞分泌γ-氨基丁酸（GABA）。
结合最近发现GABA会抑制味觉诱发的ATP分泌，目前的结果表明，SP引发了GABA的分泌，这对II型（受体）细胞提供了负反馈，以减少味觉诱发的ATP分泌。这些发现与SP作为一种抑制性递质的作用一致，即在味蕾中味觉信息处理过程中，通过GABA能信号传导塑造外周味觉信号。值得注意的是，结果表明SP在哺乳动物味觉信号处理中与GABA密切相关，并证明了味蕾内感觉信息流的一条意外途径。
