The plasma membrane monoamine transporter (PMAT) is a low-affinity

monoamine transporter Monoamine transporters (MATs) are protein structures that function as integral plasma-membrane transporters to regulate concentrations of extracellular monoamine neurotransmitters. Three major classes of MATs (SERT, DAT, NET) are responsible fo ...

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, res ...

which in humans is encoded by the ''SLC29A4''

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 b ...

. It is known alternatively as the human equilibrative nucleoside transporter-4 (hENT4). Unlike other members of the

ENT Ents are a species of beings in J. R. R. Tolkien's fantasy world Middle-earth who closely resemble trees; their leader is Treebeard of Fangorn forest. Their name is derived from an Old English word for giant. The Ents appear in ''The Lor ...

family, it is impermeable to most

nucleoside Nucleosides are glycosylamines that can be thought of as nucleotides without a phosphate group. A nucleoside consists simply of a nucleobase (also termed a nitrogenous base) and a five-carbon sugar (ribose or 2'-deoxyribose) whereas a nucleoti ...

s, with the exception of the inhibitory neurotransmitter and

ribonucleoside A ribonucleoside is a type of nucleoside including ribose as a component. One example of a ribonucleoside is cytidine Cytidine (symbol C or Cyd) is a nucleoside molecule that is formed when cytosine is attached to a ribose ring (also known as ...

adenosine Adenosine (symbol A) is an organic compound that occurs widely in nature in the form of diverse derivatives. The molecule consists of an adenine attached to a ribose via a β-N9- glycosidic bond. Adenosine is one of the four nucleoside building ...

, which it is permeable to in a highly pH-dependent manner. This protein is an integral membrane protein that transports the monoamine neurotransmitters (

serotonin Serotonin () or 5-hydroxytryptamine (5-HT) is a monoamine neurotransmitter. Its biological function is complex and multifaceted, modulating mood, cognition, reward, learning, memory, and numerous physiological processes such as vomiting and va ...

dopamine Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic chemical of the catecholamine and phenethylamine families. Dopamine constitutes about 80% o ...

norepinephrine Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic chemical in the catecholamine family that functions in the brain and body as both a hormone and neurotransmitter. The name "noradrenaline" (from Latin '' ad ...

) as well as

, from synaptic spaces into presynaptic neurons or neighboring glial cells. It is abundantly expressed in the human brain, heart tissue, and skeletal muscle, as well as in the kidneys. It is relatively insensitive to the high affinity inhibitors (such as SSRIs) of the SLC6A monoamine transporters (SERT, DAT, NET), as well being only weakly sensitive to the adenosine transport inhibitor,

dipyridamole Dipyridamole (trademarked as Persantine and others) is a nucleoside transport inhibitor and a PDE3 inhibitor medication that inhibits blood clot formation when given chronically and causes blood vessel dilation when given at high doses over a ...

. Its transport of monoamines, unlike for adenosine, is pH-insensitive. At low pH, (5.5-6.5 range, as occurs under

ischemic Ischemia or ischaemia is a restriction in blood supply to any tissue, muscle group, or organ of the body, causing a shortage of oxygen that is needed for cellular metabolism (to keep tissue alive). Ischemia is generally caused by problems w ...

conditions) however, its transport efficiency for adenosine becomes greater than for serotonin. It has 530 amino acid residues with 10–12 transmembrane segments, and is not homologous to other known monoamine transporters, such as the high-affinity SERT, DAT, and NET, or the low-affinity SLC22A OCT family. It was initially identified by a search of the draft human genome database by its sequence homology to ENTs (equilibrative nucleoside transporters).

Ligands

Inhibitors

No highly selective PMAT inhibitors are yet available, but a number of existing compounds have been found to act as weak inhibitors of this transporter, with the exception of

decynium-22 Decynium-22 is a cationic derivative of quinoline, and a potent inhibitor of the plasma membrane monoamine transporter (PMAT), as well as all members of the organic cation transporter (OCT) family in both human and rat cells. However, it has li ...

, which is more potent. These compounds include: *

Luteolin Luteolin is a flavone, a type of flavonoid, with a yellow crystalline appearance. Luteolin is the principal yellow dye compound that is obtained from the plant ''Reseda luteola'', which has been used as a source of the dye since at least the fi ...

Cimetidine Cimetidine, sold under the brand name Tagamet among others, is a histamine H2 receptor antagonist that inhibits stomach acid production. It is mainly used in the treatment of heartburn and peptic ulcers. The development of longer-acting H2 r ...

Decynium-22 Decynium-22 is a cationic derivative of quinoline, and a potent inhibitor of the plasma membrane monoamine transporter (PMAT), as well as all members of the organic cation transporter (OCT) family in both human and rat cells. However, it has li ...

Dipyridamole Dipyridamole (trademarked as Persantine and others) is a nucleoside transport inhibitor and a PDE3 inhibitor medication that inhibits blood clot formation when given chronically and causes blood vessel dilation when given at high doses over a ...

Quinidine Quinidine is a class I antiarrhythmic agent, class IA antiarrhythmic agent used to treat heart rhythm disturbances. It is the enantiomer of Antimalarial medication, antimalarial agent quinine, originally derived from the bark of the cinchona tre ...

Quinine Quinine is a medication used to treat malaria and babesiosis. This includes the treatment of malaria due to '' Plasmodium falciparum'' that is resistant to chloroquine when artesunate is not available. While sometimes used for nocturnal leg ...

Tryptamine Tryptamine is an indolamine metabolite of the essential amino acid, tryptophan. The chemical structure is defined by an indole ─ a fused benzene and pyrrole ring, and a 2-aminoethyl group at the second carbon (third aromatic atom, with the f ...

* Verapamil

Substrates

Acetylcholine Acetylcholine (ACh) is an organic chemical that functions in the brain and body of many types of animals (including humans) as a neurotransmitter. Its name is derived from its chemical structure: it is an ester of acetic acid and choline. Par ...

(poor) *

Adenosine Adenosine (symbol A) is an organic compound that occurs widely in nature in the form of diverse derivatives. The molecule consists of an adenine attached to a ribose via a β-N9- glycosidic bond. Adenosine is one of the four nucleoside building ...

(at low pH) *

Dopamine Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic chemical of the catecholamine and phenethylamine families. Dopamine constitutes about 80% o ...

Epinephrine Adrenaline, also known as epinephrine, is a hormone and medication which is involved in regulating visceral functions (e.g., respiration). It appears as a white microcrystalline granule. Adrenaline is normally produced by the adrenal glands and ...

Histamine Histamine is an organic nitrogenous compound involved in local immune responses, as well as regulating physiological functions in the gut and acting as a neurotransmitter for the brain, spinal cord, and uterus. Since histamine was discover ...

(poor) *

Metformin Metformin, sold under the brand name Glucophage, among others, is the main first-line medication for the treatment of type 2 diabetes, particularly in people who are overweight. It is also used in the treatment of polycystic ovary syndrome. ...

(poor, pH-dependent) * MPP⁺ *

Norepinephrine Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic chemical in the catecholamine family that functions in the brain and body as both a hormone and neurotransmitter. The name "noradrenaline" (from Latin '' ad ...

Serotonin Serotonin () or 5-hydroxytryptamine (5-HT) is a monoamine neurotransmitter. Its biological function is complex and multifaceted, modulating mood, cognition, reward, learning, memory, and numerous physiological processes such as vomiting and va ...

References

Membrane proteins Neurotransmitter transporters Solute carrier family Molecular neuroscience {{membrane-protein-stub

Ligands

Inhibitors

Substrates

See also

References