Department of Experimental Medicine, Pharmacology Division, University of Campania "L. Vanvitelli", Naples, Italy.
Department of Plastic Surgery, University of Campania "L. Vanvitelli", Naples, Italy.
Curr Neuropharmacol. 2020;18(2):120-125. doi: 10.2174/1570159X17666191001141849.
It is a common opinion that metabotropic glutamate receptor subtype 6 (mGluR6) is expressed exclusively in the retina, and in particular in the dendrites of ON-bipolar cells. Glutamate released in darkness from photoreceptors activates mGluR6, which is negatively associated with a membrane non-selective cation channel, the transient receptor potential melanoma-related 1, TRPM1, resulting in cell hyperpolarization. The evidence that mGluR6 is expressed not only in the retina but also in other tissues and cell populations has accumulated over time. The expression of mGluR6 has been identified in microglia, bone marrow stromal and prostate cancer cells, B lymphocytes, melanocytes and keratinocytes and non-neural tissues such as testis, kidney, cornea, conjunctiva, and eyelid. The receptor also appears to be expressed in brain areas, such as the hypothalamus, cortex, hippocampus, nucleus of tractus solitarius, superior colliculus, axons of the corpus callosum and accessory olfactory bulb. The pharmacological activation of mGluR6 in the hippocampus produced an anxiolytic-like effect and in the periaqueductal gray analgesic potential. This review aims to collect all the evidence on the expression and functioning of mGluR6 outside the retina that has been accumulated over the years for a broader view of the potential of the receptor whose retinal confinement appears understimated.
普遍认为代谢型谷氨酸受体亚型 6（mGluR6）仅在视网膜中表达，特别是在 ON-双极细胞的树突中表达。在黑暗中从光感受器释放的谷氨酸激活 mGluR6，mGluR6 与瞬时受体电位黑色素相关 1（TRPM1）形成负相关，TRPM1 是一种非选择性阳离子通道，导致细胞超极化。mGluR6 不仅在视网膜中表达，而且在其他组织和细胞群体中表达的证据随着时间的推移而积累。mGluR6 的表达已在小胶质细胞、骨髓基质和前列腺癌细胞、B 淋巴细胞、黑素细胞和角质形成细胞以及非神经组织（如睾丸、肾脏、角膜、结膜和眼睑）中得到鉴定。该受体似乎也在大脑区域（如下丘脑、皮质、海马体、孤束核、上丘、胼胝体轴突和副嗅球）中表达。在海马体中，mGluR6 的药理学激活产生了类似抗焦虑的作用，在导水管周围灰质中具有镇痛潜力。这篇综述旨在收集多年来在视网膜外积累的关于 mGluR6 表达和功能的所有证据，以便更全面地了解该受体的潜力，而该受体在视网膜中的局限似乎被低估了。
