Plasma membrane monoamine transporter
Encyclopedia
The plasma membrane monoamine transporter (PMAT) is a low-affinity monoamine transporter
protein
. It is also known as human equilibrative nucleoside transporter-4 (hENT4). Unlike other members of the ENT
family, it is impermeable to most nucleosides, with the exception of the inhibitory neurotransmitter and ribonucleoside
adenosine, which it is permeable to in a highly pH-dependent manner.
This protein is an integral membrane protein that transports the monoamine neurotransmitters (serotonin
, dopamine
, norepinephrine
) as well as adenosine, 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
. Its transport of monoamines, unlike for adenosine, is pH-insensitive. At low pH, (5.5-6.5 range, as occurs under ischemic
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).
Monoamine transporter
Monoamine transporters are protein structures that function as integral plasma membrane transporters to regulate concentrations of extracellular monoamine neurotransmitters. Three major classes of MATs are responsible for the reuptake of their associated amine neurotransmitters...
protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
. It is also known as human equilibrative nucleoside transporter-4 (hENT4). Unlike other members of the ENT
Nucleoside transporter
Nucleoside transporters are a group of membrane transport proteins which transport nucleoside substrates like adenosine across the membranes of cells and/or vesicles...
family, it is impermeable to most nucleosides, with the exception of the inhibitory neurotransmitter and ribonucleoside
Ribonucleoside
A ribonucleoside is a type of nucleoside including ribose as a component.An example is cytidine....
adenosine, 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
Serotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...
, dopamine
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...
, norepinephrine
Norepinephrine
Norepinephrine is the US name for noradrenaline , a catecholamine with multiple roles including as a hormone and a neurotransmitter...
) as well as adenosine, 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
Dipyridamole is a drug that inhibits thrombus formation when given chronically and causes vasodilation when given at high doses over a short time.-Mechanism and effects:...
. Its transport of monoamines, unlike for adenosine, is pH-insensitive. At low pH, (5.5-6.5 range, as occurs under ischemic
Ischemia
In medicine, ischemia is a restriction in blood supply, generally due to factors in the blood vessels, with resultant damage or dysfunction of tissue. It may also be spelled ischaemia or ischæmia...
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).
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.- quinidineQuinidineQuinidine is a pharmaceutical agent that acts as a class I antiarrhythmic agent in the heart. It is a stereoisomer of quinine, originally derived from the bark of the cinchona tree.-Mechanism:...
- quinineQuinineQuinine is a natural white crystalline alkaloid having antipyretic , antimalarial, analgesic , anti-inflammatory properties and a bitter taste. It is a stereoisomer of quinidine which, unlike quinine, is an anti-arrhythmic...
- verapamilVerapamilVerapamil is an L-type calcium channel blocker of the phenylalkylamine class. It has been used in the treatment of hypertension, angina pectoris, cardiac arrhythmia, and most recently, cluster headaches. It is also an effective preventive medication for migraine...
- tryptamineTryptamineTryptamine is a monoamine alkaloid found in plants, fungi, and animals. It is based around the indole ring structure, and is chemically related to the amino acid tryptophan, from which its name is derived...
- cimetidineCimetidineCimetidine INN is a histamine H2-receptor antagonist that inhibits the production of acid in the stomach. It is largely used in the treatment of heartburn and peptic ulcers. It is marketed by GlaxoSmithKline under the trade name Tagamet...
- dipyridamoleDipyridamoleDipyridamole is a drug that inhibits thrombus formation when given chronically and causes vasodilation when given at high doses over a short time.-Mechanism and effects:...
Substrates
- MPP+MPP+MPP+ is a positively charged molecule with chemical formula C12H12N+. It is toxic and acts by interfering with oxidative phosphorylation in mitochondria, causing depletion of ATP and cell death...
- DopamineDopamineDopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...
- NorepinephrineNorepinephrineNorepinephrine is the US name for noradrenaline , a catecholamine with multiple roles including as a hormone and a neurotransmitter...
- EpinephrineEpinephrineEpinephrine is a hormone and a neurotransmitter. It increases heart rate, constricts blood vessels, dilates air passages and participates in the fight-or-flight response of the sympathetic nervous system. In chemical terms, adrenaline is one of a group of monoamines called the catecholamines...
- Adenosine (at low pH)
- HistamineHistamineHistamine is an organic nitrogen compound involved in local immune responses as well as regulating physiological function in the gut and acting as a neurotransmitter. Histamine triggers the inflammatory response. As part of an immune response to foreign pathogens, histamine is produced by...
(poor) - AcetylcholineAcetylcholineThe chemical compound acetylcholine is a neurotransmitter in both the peripheral nervous system and central nervous system in many organisms including humans...
(poor) - MetforminMetforminMetformin is an oral antidiabetic drug in the biguanide class. It is the first-line drug of choice for the treatment of type 2 diabetes, in particular, in overweight and obese people and those with normal kidney function. Its use in gestational diabetes has been limited by safety concerns...
(poor, pH-dependent)