TRPV1 channels as a newly identified target for vitamin D

Abstract

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.

Hypovitaminosis D, objective oral dryness, and fungal hyphae as three precipitating factors for a subset of secondary burning mouth syndrome

“…Vitamin D is an endogenous partial agonist of the transient receptor-potential cation channel subfamily V member 1 (TRPV1) and binds with the vanilloid-binding pocket to initiate calcium-induced desensitization of pain signals [ 23 ]. TRPV1 is a Vanilloid receptor subtype −1 (VR-1) present at the nerve endings of unmyelinated C-fibers that are responsible for sensing burning sensations.…”

Mitochondrial potassium channels: A novel calcitriol target

“…Transient receptor potential cation channels (TRPV) are best described in the context of calcitriol regulation due to their contribution to cell proliferation and regulation of calcium influx. In general, calcitriol treatment increases the expression level of TRPV1 [23,24], TRPV5 [25], and TRPV6 [26]. Interestingly, the opposite effect has been observed in studies of potassium channels Kv10.1 [27,28] and TASK-1 [29].…”

A Comprehensive Review on the Regulatory Action of TRP Channels: A Potential Therapeutic Target for Nociceptive Pain

“…48 Recent studies have demonstrated vitamin D playing the role of a partial agonist of TRPV1 at physiologically relevant free plasma levels. 49,50 Parallely, several TRPV1 antagonists have also been deciphered, that have been developed as clinical lead candidates. However, their efficacies exhibited variations in preclinical models of pain.…”

“… 48 Recent studies have demonstrated vitamin D playing the role of a partial agonist of TRPV1 at physiologically relevant free plasma levels. 49 , 50 …”