The functions of TRPA1 and TRPV1: moving away from sensory nerves

Abstract

The transient receptor potential vanilloid 1 and ankyrin 1 (TRPV1 and TRPA1, respectively) channels are members of the TRP superfamily of structurally related, non-selective cation channels. It is rapidly becoming clear that the functions of TRPV1 and TRPA1 interlink with each other to a considerable extent. This is especially clear in relation to pain and neurogenic inflammation where TRPV1 is coexpressed on the vast majority of TRPA1-expressing sensory nerves and both integrate a variety of noxious stimuli. The more recent discovery that both TRPV1 and TRPA1 are expressed on a multitude of non-neuronal sites has led to a plethora of research into possible functions of these receptors. Non-neuronal cells on which TRPV1 and TRPA1 are expressed vary from vascular smooth muscle to keratinocytes and endothelium. This review will discuss the expression, functionality and roles of these non-neuronal TRP channels away from sensory nerves to demonstrate the diverse nature of TRPV1 and TRPA1 in addition to a direct role in pain and neurogenic inflammation. AbbreviationsPBMC, peripheral blood mononuclear cell; TRPA1, transient receptor potential cation channel subfamily A member 1; TRPV1, transient receptor potential cation channel subfamily V member 1

N-Arachidonoyl Dopamine Modulates Acute Systemic Inflammation via Nonhematopoietic TRPV1

“…Consistent with the cumulative evidence that points to a protective role for TRPV1 in murine sepsis models, we observe that TRPV1 activation displays a protective phenotype of reduced proinflammation, increased anti-inflammation, and downregulation of PAI-1 in toxicity and infection models of sepsis (17,27,39,40). However, in contrast to other reports on TRPV1 in sepsis, we did not detect differences in the cytokine responses of Trpv1 2/2 and WT mice treated with LPS or Pam3Cys in the absence of NADA.…”

“…The majority of the in vivo work on NADA has focused on its neurologic and behavioral effects, and NADA's effects on inflammation have not been characterized (2,(35)(36)(37)(38). Although there are mixed studies suggesting that TRPV1 activation affects inflammation in models of sepsis, to our knowledge, no prior study has investigated in vivo the role of NADA or the NADA-TRPV1 axis in sepsis (17,27,39,40). Therefore, we tested the hypothesis that the administration of NADA would reduce acute systemic inflammation in sepsis via activation of TRPV1.…”

“…TRPV1 is also expressed in the CNS, including the spinal cord, striatum, hippocampus, cerebellum, and amygdala (19)(20)(21)(22)(23). Finally, TRPV1 is found in nonneuronal cells, including leukocytes, smooth muscle cells, and endothelial cells (11,17,(24)(25)(26)(27). In this regard, TRPV1 activation has been reported to regulate the activation and proinflammatory properties of CD4 + T cells (28) NADA and TRPV1 have overlapping distributions, because NADA has been detected in the striatum, cerebellum, hippocampus, thalamus, brainstem, and dorsal root ganglia (7,19,20,23,29).…”

Un nouveau rôle pour le canal ionique TRPV1 dans l’activation des lymphocytes T CD4

“…Depuis sa découverte, TRPV1 a principalement été étudié dans le système nerveux périphé-rique et il a été établi que ce canal joue un rôle prépondérant dans la perception de la douleur. Cependant, il est très exprimé dans le corps en dehors des systèmes nerveux central et périphérique, par exemple dans la peau, l'appareil digestif, et le système immunitaire [6,8]. Ainsi, nous avons récemment découvert l'expression des canaux TRPV1 à la surface des LT CD4 et leur rôle dans l'entrée de Ca 2+ dans ces cellules dans des conditions physiologique et pathologique [9].…”

Novel immune function for the TRPV1 channel in T lymphocytes

“…1 Although TRPV1 is well characterized in peripheral sensory neurons as a pain receptor, growing evidence suggests that TRPV1 has functional roles in many other organs and cells, including those of the immune system. 2 The current paradigm of Ca 2C entry in CD4-positive T lymphocytes (CD4 C T cells) is mostly centered on store operated Ca 2C entry (SOCE). 3 In this model, Tcell receptor (TCR) stimulation induces a cascade of signaling events that leads to the activation of phospholipase C gamma 1 (PLC-g1), which catabolizes phosphatidylinositol-4,5-bisphosphate (PIP 2 ) into diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP 3 ).…”