Plasma membrane monoamine transporter
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).
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.
- Adenosine (at low pH)
- Histamine (poor)
- Acetylcholine (poor)
- Metformin (poor, pH-dependent)
- Xia L, Zhou M, Kalhorn TF, Ho HT, Wang J. Podocyte-specific expression of organic cation transporter PMAT: implication in puromycin aminonucleoside nephrotoxicity. American Journal of Physiology. Renal Physiology. 2009 Jun;296(6):F1307-13. PMID 19357181
- Dahlin A, Xia L, Kong W, Hevner R, Wang J. Expression and immunolocalization of the plasma membrane monoamine transporter in the brain. Neuroscience. 2007 May 25;146(3):1193-211. PMID 17408864
- Engel K, Zhou M, Wang J. Identification and characterization of a novel monoamine transporter in the human brain. Journal of Biological Chemistry. 2004 Nov 26;279(48):50042-9. doi:10.1074/jbc.M407913200 PMID 15448143
- Engel K, Wang J. Interaction of organic cations with a newly identified plasma membrane monoamine transporter. Molecular Pharmacology. 2005 Nov;68(5):1397-407. doi:10.1124/mol.105.016832 PMID 16099839