Transient receptor potential cation channel subfamily M member 5 (TRPM5), also known as long transient receptor potential channel 5 is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...

that in humans is encoded by the ''TRPM5''

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...

Function

TRPM5 is a calcium-activated non-selective cation channel that induces depolarization upon increases in intracellular calcium, it is a signal mediator in chemosensory cells. Channel activity is initiated by a rise in the intracellular calcium, and the channel permeates monovalent cations as K⁺ and Na⁺. TRPM5 is a key component of

taste The gustatory system or sense of taste is the sensory system that is partially responsible for the perception of taste (flavor). Taste is the perception produced or stimulated when a substance in the mouth reacts chemically with taste receptor ...

transduction in the

gustatory system The gustatory system or sense of taste is the sensory system that is partially responsible for the perception of taste (flavor). Taste is the perception produced or stimulated when a substance in the mouth reacts chemically with taste receptor ...

bitter Bitter may refer to: Common uses * Resentment, negative emotion or attitude, similar to being jaded, cynical or otherwise negatively affected by experience * Bitter (taste), one of the five basic tastes Books * '' Bitter (novel)'', a 2022 nove ...

sweet Sweetness is a basic taste most commonly perceived when eating foods rich in sugars. Sweet tastes are generally regarded as pleasurable. In addition to sugars like sucrose, many other chemical compounds are sweet, including aldehydes, ketones ...

and

umami Umami ( from ja, 旨味 ), or savoriness, is one of the five basic tastes. It has been described as savory and is characteristic of broths and cooked meats. People taste umami through taste receptors that typically respond to glutamates and ...

tastes being activated by high levels of intracellular

calcium Calcium is a chemical element with the symbol Ca and atomic number 20. As an alkaline earth metal, calcium is a reactive metal that forms a dark oxide-nitride layer when exposed to air. Its physical and chemical properties are most similar to ...

. It has also been targeted as a possible contributor to fat

signaling. The calcium dependent opening of TRPM5 produces a depolarizing generator potential which leads to an

action potential An action potential occurs when the membrane potential of a specific cell location rapidly rises and falls. This depolarization then causes adjacent locations to similarly depolarize. Action potentials occur in several types of animal cells, ...

. TRPM5 is expressed in pancreatic β-cells where it is involved in the signaling mechanism for insulin secretion. The potentiation of TRPM5 in the β-cells leads to increased

insulin Insulin (, from Latin ''insula'', 'island') is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the ''INS'' gene. It is considered to be the main anabolic hormone of the body. It regulates the metabolism o ...

secretion and protects against the development of

type 2 diabetes Type 2 diabetes, formerly known as adult-onset diabetes, is a form of diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. Common symptoms include increased thirst, frequent urinatio ...

in mice. Further expression of TRPM5 can be found in

tuft cells Tuft cells are chemosensory cells in the epithelial lining of the intestines. Similar tufted cells are found in the respiratory epithelium where they are known as brush cells. The name "tuft" refers to the brush-like microvilli projecting from ...

, solitary chemosensory cells and several other cell types in the body that have a sensory role.

Drugs modulating TRPM5

The role of TRPM5 in the pancreatic β-cell makes it a target for the development of novel antidiabetic therapies.

Agonists

Steviol glycoside Steviol glycosides are the chemical compounds responsible for the sweet taste of the leaves of the South American plant '' Stevia rebaudiana'' (Asteraceae) and the main ingredients (or precursors) of many sweeteners marketed under the generic na ...

s, the sweet compounds in the leaves of the

Stevia rebaudiana ''Stevia rebaudiana'' is a plant species in the genus ''Stevia'' of the family Asteraceae. It is commonly known as candyleaf, sweetleaf or sugarleaf. It is a small seasonal plant which grows to a height of . It has elongated leaves that grow al ...

plant, potentiate the calcium-induced activity of TRPM5. In this way they stimulate the glucose-induced insulin secretion from the pancreatic β-cell. * Rutamarin, a phytochemical found in

Ruta graveolens ''Ruta graveolens'', commonly known as rue, common rue or herb-of-grace, is a species of '' Ruta'' grown as an ornamental plant and herb. It is native to the Balkan Peninsula. It is grown throughout the world in gardens, especially for its blui ...

has been identified as an activator of several TRP channels, including TRPM5 and

TRPV1 The transient receptor potential cation channel subfamily V member 1 (TrpV1), also known as the capsaicin receptor and the vanilloid receptor 1, is a protein that, in humans, is encoded by the ''TRPV1'' gene. It was the first isolated member of th ...

and inhibits the activity of

TRPM8 Transient receptor potential cation channel subfamily M (melastatin) member 8 (TRPM8), also known as the cold and menthol receptor 1 (CMR1), is a protein that in humans is encoded by the ''TRPM8'' gene. The TRPM8 channel is the primary molecular ...

Antagonists

Selective blocking agents of TRPM5 ion channels can be used to identify TRPM5 currents in primary cells. Most identified compounds show, however, a poor selectivity between

TRPM4 Transient receptor potential cation channel subfamily M member 4 (hTRPM4), also known as melastatin-4, is a protein that in humans is encoded by the TRPM4 gene. TRPM4 Channel Blocker * 9-Phenanthrol * TRPM4-IN-5 See also * TRPM TRPM is a family ...

and TRPM5 or other ion channels. * TPPO or TriPhenylPhosphineOxide is the most selective blocker of TRPM5 however, its application suffers due to a poor solubility. * Ketoconazole is an antifungal drug that inhibits TRPM5 activity. *

Flufenamic Acid Flufenamic acid (FFA) is a member of the anthranilic acid derivatives (or fenamate) class of nonsteroidal anti-inflammatory drugs (NSAIDs). Like other members of the class, it is a cyclooxygenase (COX) inhibitor, preventing the formation of pr ...

is an

NSAID Non-steroidal anti-inflammatory drugs (NSAID) are members of a therapeutic drug class which reduces pain, decreases inflammation, decreases fever, and prevents blood clots. Side effects depend on the specific drug, its dose and duration of ...

drug that inhibits the activity of TRPM5 or TRPM4. *

Clotrimazole Clotrimazole, sold under the brand name Lotrimin, among others, is an antifungal medication. It is used to treat vaginal yeast infections, oral thrush, diaper rash, tinea versicolor, and types of ringworm including athlete's foot and jock i ...

is an antifungal drug and reduces the currents through TRPM5. *

Nicotine Nicotine is a natural product, naturally produced alkaloid in the nightshade family of plants (most predominantly in tobacco and ''Duboisia hopwoodii'') and is widely used recreational drug use, recreationally as a stimulant and anxiolytic. As ...

inhibits the TRPM5 channel. Through the inhibition of TRPM5, the taste loss observed in people with a smoking habit can be explained.

References

External links

*
IUPHAR

HGNC Gene families

Pfam
{{Transient receptor potential channel modulators Ion channels