Department of Pharmacology and the Alberta Diabetes Institute, University of Alberta, Edmonton, Canada.
Department of Chemistry, University of Waterloo, Waterloo, Canada.
Channels (Austin). 2021 Dec;15(1):360-374. doi: 10.1080/19336950.2021.1905248.
Vitamin D is known to elicit many biological effects in diverse tissue types and is thought to act almost exclusively upon its canonical receptor within the nucleus, leading to gene transcriptional changes and the subsequent cellular response. However, not all the observed effects of vitamin D can be attributed to this sole mechanism, and other cellular targets likely exist but remain to be identified. Our recent discovery that vitamin D is a partial agonist of the Transient Receptor Potential Vanilloid family 1 (TRPV1) channel may provide new insights as to how this important vitamin exerts its biological effects either independently or in addition to the nuclear vitamin D receptor. In this review, we discuss the literature surrounding this apparent discrepancy in vitamin D signaling and compare vitamin D with known TRPV1 ligands with respect to their binding to TRPV1. Furthermore, we provide evidence supporting the notion that this novel vitamin D/TRPV1 axis may explain some of the beneficial actions of this vitamin in disease states where TRPV1 expression and vitamin D deficiency are known to overlap. Finally, we discuss whether vitamin D may also act on other members of the TRP family of ion channels.
维生素 D 被认为在多种组织类型中引发多种生物学效应，并且几乎仅在其核内的经典受体上起作用，导致基因转录变化和随后的细胞反应。然而，并非维生素 D 的所有观察到的作用都可以归因于这种单一机制，并且可能存在其他细胞靶标，但仍有待确定。我们最近的发现表明，维生素 D 是瞬时受体电位香草酸家族 1（TRPV1）通道的部分激动剂，这可能为这种重要维生素如何独立于核维生素 D 受体或除核维生素 D 受体之外发挥其生物学作用提供新的见解。在这篇综述中，我们讨论了围绕维生素 D 信号的这种明显差异的文献，并比较了维生素 D 与已知的 TRPV1 配体在与 TRPV1 结合方面的情况。此外，我们提供了证据支持这样一种观点，即这种新的维生素 D/TRPV1 轴可能解释了这种维生素在已知 TRPV1 表达和维生素 D 缺乏重叠的疾病状态下的一些有益作用。最后，我们讨论了维生素 D 是否也可能作用于其他 TRP 家族离子通道成员。
