TRPV6

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.

Transient receptor potential channel subfamily vanilloid member 6 (TRPV6) is a calcium-permeable channel (Peng et al. 2000) involved in neurotransmission, muscle contraction, and exocytosis by "providing" dietary calcium as an intracellular second messenger. Depending on the tissue, transcellular calcium transport can be regulated by vitamin D, parathyroid hormone (PTH) or calcitonin. This controls the body's requirement for Ca(2+) under various physiological conditions such as Ca(2+)-deficient diets, pregnancy, lactation, exercise and aging, as well as pathological and therapeutic conditions.

The coding TRPV6 gene is located on chromosome 7q33-q34. Mutations in the TRPV6 gene lead to the clinical picture of transient neonatal hyperparathyroidism (HRPTTN; OMIM: 618188 - Suzuki et al. 2018).

Using screening methods, TRPV6 could be detected in various organs such as small intestine, pancreas and a colon cancer cell line with lower expression in kidney and small intestine (Peng et al. 2000, Barley et al. 2001, Peng 2011).

Wissenbach et al (2001) cloned and characterized TRPV6 (CATL) in trophoblasts and syncytiotrophoblasts of normal placenta.

TRPV6 transcripts could not be detected in healthy prostate tissue and benign prostatic hyperplasia, but could be detected at high levels in advanced prostate cancer, in prostate metastases and in recurrent androgen-insensitive prostate adenocarcinoma and other types of carcinoma (Peng et al. 2001, Stewart JM 2020). New therapeutic approaches may emerge in this regard.

TRPV6 appears to play a role in the etiopathogenesis of diabetes mellitus. In diabetic rats, for example, a significant increase in messenger RNA expression of TRPV5, TRPV6, TRPM6 and calbindin-D28k has been demonstrated (Lee CT et al. 2006).

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 in humans play an important role 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. It is believed that some TRP channels in the body 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, nervous, and endocrine 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)

TRPV6 is found in mammals, birds and fish, whereas TRPV5 is found only in mammals. In human and other mammalian genomes, TRPV5 and TRPV6 show complete conservation of exon size in the coding region and are adjacent to each other. TRPV5 appears to have arisen by duplication of TRPV6 during mammalian evolution from reptiles. Compared to other populations, TRPV6 has high levels of SNPs in African populations, indicating that TRPV6 was under selective pressure during or after human migration from Africa.

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