The thermo‐TRP ion channel family: properties and therapeutic implications

Abstract

The thermo‐transient receptor potentials (TRPs), a recently discovered family of ion channels activated by temperature, are expressed in primary sensory nerve terminals where they provide information about thermal changes in the environment. Six thermo‐TRPs have been characterised to date: TRP vanilloid (TRPV) 1 and 2 are activated by painful levels of heat, TRPV3 and 4 respond to non‐painful warmth, TRP melastatin 8 is activated by non‐painful cool temperatures, while TRP ankyrin (TRPA) 1 is activated by painful cold. The thermal thresholds of many thermo‐TRPs are known to be modulated by extracellular mediators, released by tissue damage or inflammation, such as bradykinin, PG and growth factors. There have been intensive efforts recently to develop antagonists of thermo‐TRP channels, particularly of the noxious thermal sensors TRPV1 and TRPA1. Blockers of these channels are likely to have therapeutic uses as novel analgesics, but may also cause unacceptable side effects. Controlling the modulation of thermo‐TRPs by inflammatory mediators may be a useful alternative strategy in developing novel analgesics.

Presynaptic TRPV1 vanilloid receptor function is age- but not CB1 cannabinoid receptor-dependent in the rodent forebrain

“…Capsaicin is a well-established and potent agonist for the TRPV 1 R (Caterina et al, 1997). ACEA, however, possesses additional putative binding sites including the TRPV 4 R channel (Vay et al, 2012) and intracellular targets (Köfalvi, 2008). Hence, these conflicting data here do not support the hypothesis that CB 1 Rs keep putative TRPV 1 Rs silent in serotonergic terminals.…”

Human Sensory Neuron-specific Mas-related G Protein-coupled Receptors-X1 Sensitize and Directly Activate Transient Receptor Potential Cation Channel V1 via Distinct Signaling Pathways

“…A major drawback for the use of TRPV1 blockers in clinical trials is increased core body temperature (10,58). A recent study set out to correlate the effects of various TRPV1 blockers on heat-and proton-induced TRPV1 activation with their concomitant influence on body temperature in rats and mice.…”

The Mammalian Circadian Timing System: Synchronization of Peripheral Clocks

“…Moreover, the depletion of HSF2 via RNA interference had no effect on the temperaturedependent synchronization of the clocks operative in these cells. Hence, we believe that temperature sensors other than HSFs, forexample, thermosensitive transient receptor potential channels (thermoTRPs) (Vay et al 2011), may participate in this process.…”