The plasma membrane monoamine transporter (PMAT): Structure, function, and role in organic cation disposition

Wang, Joanne

doi:10.1002/cpt.442

Cited by 58 publications

(57 citation statements)

References 72 publications

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“…29) PMAT is a relatively new organic cation transporter, originally cloned from the human brain. 29) PMAT has been shown to exhibit similar transporter characteristics to those of OCT3 (for more details, please see the review article 30) ). Like OCT3, PMAT can transport MPP + , dopamine, norepinephrine, epinephrine, 5-HT, and histamine, and is strongly inhibited by D22.…”

Section: Plasma Membrane Monoamine Transporter (Pmat)mentioning

confidence: 99%

“…Like OCT3, PMAT can transport MPP + , dopamine, norepinephrine, epinephrine, 5-HT, and histamine, and is strongly inhibited by D22. 29,30) However, it should be noted that the substrate preference of PMAT is different from that of OCT3: OCT3 exhibits higher transport activity levels towards norepinephrine, epinephrine, and histamine, whereas PMAT prefers to transport dopamine and 5-HT. 24) This difference suggests that the role of PMAT in the clearance of biogenic amines at synapses is different from that of OCT3.…”

Section: Plasma Membrane Monoamine Transporter (Pmat)mentioning

confidence: 99%

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Functional Expression of Organic Ion Transporters in Astrocytes and Their Potential as a Drug Target in the Treatment of Central Nervous System Diseases

Furihata

Anzai

2017

Biological & Pharmaceutical Bulletin

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It has become widely acknowledged that astrocytes play essential roles in maintaining physiological central nervous system (CNS) activities. Astrocytes fulfill their roles partly through the manipulation of their plasma membrane transporter functions, and therefore these transporters have been regarded as promising drug targets for various CNS diseases. A representative example is excitatory amino acid transporter 2 (EAAT2), which works as a critical regulator of excitatory signal transduction through its glutamate uptake activity at the tripartite synapse. Thus, enhancement of EAAT2 functionality is expected to accelerate glutamate clearance at synapses, which is a promising approach for the prevention of over-excitation of glutamate receptors. In addition to such well-known astrocyte-specific transporters, cumulative evidence suggests that multi-specific organic ion transporters (i.e., organic cation/anion transporters [OCTs/OATs], carnitine/organic cation transporters [OCTNs], and organic anion transporting polypeptides [OATPs]) are also functionally expressed in astrocytes. Even though identification and characterization of their physiological/pathophysiological roles in astrocytes are in the initial stage, the findings obtained so far indicate that OCT3 and plasma membrane monoamine transporter are significantly involved in the clearance of biogenic amine neurotransmitters in the synaptic cleft, and that OCTN2 and OATP1C1 provide a cellular entry gate for carnitine/acetyl-L-carnitine and thyroxine, respectively. Therefore, organic ion transporters, including those mentioned above, are expected to become emerging pharmacological targets for various CNS diseases. With such expectations in mind, this review will briefly summarize the functional expression of organic ion transporters in astrocytes.

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Section: Plasma Membrane Monoamine Transporter (Pmat)mentioning

confidence: 99%

Section: Plasma Membrane Monoamine Transporter (Pmat)mentioning

confidence: 99%

Functional Expression of Organic Ion Transporters in Astrocytes and Their Potential as a Drug Target in the Treatment of Central Nervous System Diseases

Furihata

Anzai

2017

Biological & Pharmaceutical Bulletin

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“…SLC29A4 encodes for an integral plasma membrane protein known as PMAT (Plasma Membrane Monoamine Transporter) or ENT4 (Equilibrative Nucleoside Transporter 4). ENT4 differs from ENTs encoded by other members of the SLC29 family (ENT1, ENT2, ENT3) in that it also transports monoamines such as 5‐hydroxytryptamine (5‐HT; Engel, Zhou, & Wang, 2004; Shirasaka et al, 2017; Wang, 2016). Furthermore, it has a more restricted specificity for nucleosides than other ENTs, accepting only adenosine and some adenosine analogues (Tandio, Vilas, & Hammond, 2019) as substrates.…”

Section: Introductionmentioning

confidence: 99%

Deletion of murine slc29a4 modifies vascular responses to adenosine and 5‐hydroxytryptamine in a sexually dimorphic manner

et al. 2020

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Equilibrative nucleoside transporter 4 (ENT4), encoded by SLC29A4, mediates the flux of both 5‐hydroxytryptamine (5‐HT) and adenosine across cell membranes. We hypothesized that loss of ENT4 function in mice would modify the effects of these established regulators of vascular function. Male and female wild‐type (WT) and slc29a4‐null (ENT4‐KO) mice were compared with respect to their hemodynamics and mesenteric vascular function. Male ENT4‐KO mice had a complete loss of myogenic tone in their mesenteric resistance arteries. This was accompanied by a decrease in blood flow in the superior mesenteric artery in the male ENT4‐KO mice, and a reduced responsiveness to 5‐HT. In contrast, endothelium‐dependent relaxations of mesenteric arteries from female ENT4‐KO mice were more sensitive to Ca2+‐activated K+ (KCa) channel blockade than WT mice. Female ENT4‐KO mice also demonstrated an enhanced vasodilatory response to adenosine in vivo that was not seen in males. Ketanserin (5‐HT2A inhibitor) and GR55562 (5‐HT1B/1D inhibitor) decreased 5‐HT‐induced tone, but only ketanserin inhibited the relaxant effect of 5‐HT in mesenteric arteries. 5‐HT‐evoked increases in tone were elevated in arteries from ENT4‐KO mice upon block of endothelial relaxant pathways, with arteries from female ENT4‐KO mice showing the greatest increase. Adenosine A2b receptor expression was decreased, while other adenosine transporter subtypes, as well as adenosine deaminase and adenosine kinase were increased in mesenteric arteries from male, but not female, ENT4‐KO mice. These findings indicate that deletion of slc29a4 leads to sex‐specific changes in vascular function with significant consequences for regulation of blood flow and pressure by adenosine and 5‐HT.

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“…We used decynium‐22 (100 µM highest dose) to inhibit fluoxetine‐resistant 5‐HT transporters. This compound has been reported to inhibit PMAT and OCT3 with equal potency (Ki; 0.1 mM; Engel & Wang, ; Hayer‐Zillgen et al, ; Wang, ). We also used corticosterone (1 mM highest dose), which has been reported to be more selective toward OCTs with IC50 values in 0.29–34 mM for human OCT1‐3 (Hayer‐Zillgen et al, ), to differentiate the contribution of PMAT and OCTs on 5‐HT transport.…”

Section: Discussionmentioning

confidence: 99%

Serotonin uptake via plasma membrane monoamine transporter during myocardial ischemia‐reperfusion in the rat heart in vivo

Sonobe

Akiyama

et al. 2019

Physiol Rep

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Serotonin (5‐HT) accumulates in the heart during myocardial ischemia and induces deleterious effects on the cardiomyocytes through receptor‐dependent and monoamine oxidase‐dependent pathways. We aimed to clarify the involvement of extra‐neuronal monoamine transporters in the clearance of 5‐HT during ischemia and reperfusion in the heart. Using a microdialysis technique in the anesthetized Wistar rat heart, we monitored myocardial interstitial 5‐HT and 5‐hydroxyindole acetic acid (5‐HIAA) concentration by means of electro‐chemical detection coupled with high‐performance liquid chromatography (HPLC‐ECD). Effects of inhibitors of the plasma membrane monoamine transporter (PMAT) and the organic cation transporter 3 (OCT3) (decynium‐22 and corticosterone) on the 5‐HT and 5‐HIAA concentrations during baseline, coronary occlusion, and reperfusion were investigated. Basal dialysate 5‐HT concentration were increased by local administration of decynium‐22, but not by corticosterone. Addition of fluoxetine, a serotonin transporter (SERT) inhibitor further increased the 5‐HT concentration upon during administration of decynium‐22. Decynium‐22 elevated the background level of 5‐HT during coronary occlusion and maintained 5‐HT concentration at a high level during reperfusion. Production of 5‐HIAA in the early reperfusion was significantly suppressed by decynium‐22. These results indicate that PMAT and SERT independently regulate basal level of interstitial 5‐HT, and PMAT plays a more important role in the clearance of 5‐HT during reperfusion. These data suggest the involvement of PMAT in the monoamine oxidase‐dependent deleterious pathway in the heart.

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The plasma membrane monoamine transporter (PMAT): Structure, function, and role in organic cation disposition

Cited by 58 publications

References 72 publications

Functional Expression of Organic Ion Transporters in Astrocytes and Their Potential as a Drug Target in the Treatment of Central Nervous System Diseases

Functional Expression of Organic Ion Transporters in Astrocytes and Their Potential as a Drug Target in the Treatment of Central Nervous System Diseases

Deletion of murine slc29a4 modifies vascular responses to adenosine and 5‐hydroxytryptamine in a sexually dimorphic manner

Serotonin uptake via plasma membrane monoamine transporter during myocardial ischemia‐reperfusion in the rat heart in vivo

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