TRPV5

TRP channels are phylogenetically early signaling pathways (they can already be detected in yeast cells). The first TRP channel was identified in 1989 in connection with visual perception in Drosophila melanogaster. In a Drosophila mutant (trp343), it was shown that its photoreceptors responded to light stimuli only with a transient, i.e. rapidly inactivating, membrane current. In the non-mutated wild type, however, the current flow persisted as long as light hit the photoreceptor. The mutant protein -TRP- was cloned in 1989. Thus, the name "transient receptor potential" - TRP- refers to the description of a phenotype of a mutant of the fruit fly Drosophila melanogaster.

The term "TRP channels" = transient receptor potential channels, summarizes a large family of cellular ion channels. In both vertebrates and non-vertebrates, TRP channels exert important functions in primary signaling pathways for the regulated influx of Ca2+ into a cell. TRP channels play important roles in humans in the sensation of different types of taste (sweet, bitter, umami) as well as in the perception of pain, heat, warmth or cold, pressure and light.

Some TRP channels in the body are thought to behave like microscopic thermosensors. To date, 28 TRP channel genes have been identified in mammals (Nilius B et al. 2011).

Some TRP channels are activated by molecules found in spices such as garlic (allicin), chili pepper (capsaicin), wasabi (allyl isothiocyanate). Others are activated by menthol, camphor, peppermint, and refrigerants. Still others are activated by molecules found in cannabis (i.e. THC, CBD, and CBN). Some act as sensors of osmotic pressure, volume, strain, and vibration. TRP channelopathies result from mutations in genes that encode TRP channels. Several inherited human diseases (so-called "TRP channelopathies") affecting the cardiovascular, renal, skeletal, and nervous systems are grouped under this name (Nilius B et al. 2011). TRP channels are also promising targets for drug development. For example, a number of potent small molecule TRPV1 channel antagonists (occasionally TRPM8 antagonists) are now showing therapeutic benefit in the treatment of inflammatory and neuropathic pain. (Moran MM et al. 2018)

Transient receptor potential channel subfamily vanilloid member 5 (TRPV5) is a calcium-selective ion channel that functions an important role in renal Ca2 + homeostasis (rate-determining regulator of calcium reabsorption) (Hughes TE et al. 2019). Intracellular Mg2 + causes rapid voltage-dependent blockade of the TRPV5 channel. Its role in nephrolithiasis is currently unclear (van der Wijst J et al 2019). TRPV5 is activated by both endogenous and exogenous stimuli (Lee J et al 2005. ). Thus, TRPV5 is involved in osteoclast (OC) differentiation. TRPV5 expression is downregulated after prolonged exposure to 1,25 (OH) 2D3 (vitamin D). This leads to inhibition of OC differentiation. Gu J et al (2019) . Furthermore, TRP V5 appears to play a role in diabetes mellitus. Thus, a significant increase in messenger RNA expression of TRP V5, TRPV6, TRPM6 as well as calbindin-D28k was detected in diabetic rats. Renal epithelia expressed more calbindin-D28k and TRPV5 in diabetes mellitus (Lee CT et al. 2006).

1. Gu J et al (2019) Vitamin D Inhibition of TRPV5 Expression During Osteoclast Differentiation. Int J Endocrinol Metab 17:e91583.
2. Hughes TE et al (2019) Structure-based characterization of novel TRPV5 inhibitors. Elife 8:e49572.
3. Lee CT et al (2006) Increased renal calcium and magnesium transporter abundance in streptozotocin-induced diabetes mellitus. Kidney Int 69:1786-1791.
4. Lee J et al (2005) PIP2 activates TRPV5 and releases its inhibition by intracellular Mg2+. J Gen Physiol 126:439-451.
5. Michalick L et al (2020) TRPV4-A Missing Link Between Mechanosensation and Immunity. Front Immunol 11:413.
6. Moran MM et al. (2018) Targeting nociceptive transient receptor potential channels to treat chronic pain: current state of the field. Br J Pharmacol 175:2185-2203.
7. Nilius B et al (2011) The transient receptor potential family of ion channels. Genome Biol 12:218.
8. van der Wijst J et al. (2019) TRPV5 in renal tubular calcium handling and its potential relevance for nephrolithiasis. Kidney Int 96:1283-1291.
9. Wang Y et al (2017) Targeting Transient Receptor Potential Canonical Channels for Diseases of the Nervous System. Curr Drug Targets.18:1460-1465.