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 residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

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

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

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. Taste is the perception stimulated when a substance in the mouth biochemistry, reacts chemically with taste receptor cells l ...

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. Taste is the perception stimulated when a substance in the mouth reacts chemically with taste receptor cells located on t ...

of bitter,

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 ), or savoriness, is one of the five basic tastes. It is characteristic of broths and cooked meats. People taste umami through taste receptors that typically respond to glutamates and nucleotides, which are widely present in me ...

tastes being activated by high levels of intracellular

calcium Calcium is a chemical element; it has 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 ...

. 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 (also known as a nerve impulse or "spike" when in a neuron) is a series of quick changes in voltage across a cell membrane. An action potential occurs when the membrane potential of a specific Cell (biology), cell rapidly ri ...

. 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 insulin (''INS)'' gene. It is the main Anabolism, anabolic hormone of the body. It regulates the metabol ...

secretion and protects against the development of

type 2 diabetes Type 2 diabetes (T2D), 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 ...

in mice. Further expression of TRPM5 can be found in tuft cells, 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 chemical precursor, precursors) of many sugar substitute, swee ...

s, the sweet compounds in the leaves of the Stevia rebaudiana 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 the genus ''Ruta'' grown as an ornamental plant and herb. It is native to the Mediterranean. It is grown throughout the world in gardens, especially for it ...

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 ...

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 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 Ketoconazole, sold under the brand name Nizoral, among others, is an antiandrogen, antifungal drug, antifungal, and antiglucocorticoid medication used to treat a number of fungal infections. Applied to the skin it is used for fungal skin inf ...

is an antifungal drug that inhibits TRPM5 activity. * Flufenamic Acid 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 itc ...

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