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

2016 ◽  
Vol 100 (5) ◽  
pp. 489-499 ◽  
Author(s):  
J Wang
2021 ◽  
Vol 22 (23) ◽  
pp. 12995
Author(s):  
Thomas J. F. Angenoorth ◽  
Stevan Stankovic ◽  
Marco Niello ◽  
Marion Holy ◽  
Simon D. Brandt ◽  
...  

Many psychoactive compounds have been shown to primarily interact with high-affinity and low-capacity solute carrier 6 (SLC6) monoamine transporters for norepinephrine (NET; norepinephrine transporter), dopamine (DAT; dopamine transporter) and serotonin (SERT; serotonin transporter). Previous studies indicate an overlap between the inhibitory capacities of substances at SLC6 and SLC22 human organic cation transporters (SLC22A1–3; hOCT1–3) and the human plasma membrane monoamine transporter (SLC29A4; hPMAT), which can be classified as high-capacity, low-affinity monoamine transporters. However, interactions between central nervous system active substances, the OCTs, and the functionally-related PMAT have largely been understudied. Herein, we report data from 17 psychoactive substances interacting with the SLC6 monoamine transporters, concerning their potential to interact with the human OCT isoforms and hPMAT by utilizing radiotracer-based in vitro uptake inhibition assays at stably expressing human embryonic kidney 293 cells (HEK293) cells. Many compounds inhibit substrate uptake by hOCT1 and hOCT2 in the low micromolar range, whereas only a few substances interact with hOCT3 and hPMAT. Interestingly, methylphenidate and ketamine selectively interact with hOCT1 or hOCT2, respectively. Additionally, 3,4-methylenedioxymethamphetamine (MDMA) is a potent inhibitor of hOCT1 and 2 and hPMAT. Enantiospecific differences of R- and S-α-pyrrolidinovalerophenone (R- and S-α-PVP) and R- and S-citalopram and the effects of aromatic substituents are explored. Our results highlight the significance of investigating drug interactions with hOCTs and hPMAT, due to their role in regulating monoamine concentrations and xenobiotic clearance.


2019 ◽  
Vol 849 ◽  
pp. 75-83 ◽  
Author(s):  
Trivadila Slamet Soetanto ◽  
Shuang Liu ◽  
Muhammad Novrizal Abdi Sahid ◽  
Kensuke Toyama ◽  
Kazutaka Maeyama ◽  
...  

2021 ◽  
Vol 22 (24) ◽  
pp. 13420
Author(s):  
Nikki J. Clauss ◽  
Wouter Koek ◽  
Lynette C. Daws

A lack of effective treatment and sex-based disparities in psychostimulant addiction and overdose warrant further investigation into mechanisms underlying the abuse-related effects of amphetamine-like stimulants. Uptake-2 transporters such as organic cation transporter 3 (OCT3) and plasma membrane monoamine transporter (PMAT), lesser studied potential targets for the actions of stimulant drugs, are known to play a role in monoaminergic neurotransmission. Our goal was to examine the roles of OCT3 and PMAT in mediating amphetamine (1 mg/kg)-induced conditioned place preference (CPP) and sensitization to its locomotor stimulant effects, in males and females, using pharmacological, decynium-22 (D22; 0.1 mg/kg, a blocker of OCT3 and PMAT) and genetic (constitutive OCT3 and PMAT knockout (−/−) mice) approaches. Our results show that OCT3 is necessary for the development of CPP to amphetamine in males, whereas in females, PMAT is necessary for the ability of D22 to prevent the development of CPP to amphetamine. Both OCT3 and PMAT appear to be important for development of sensitization to the locomotor stimulant effect of amphetamine in females, and PMAT in males. Taken together, these findings support an important, sex-dependent role of OCT3 and PMAT in the rewarding and locomotor stimulant effects of amphetamine.


2012 ◽  
Vol 40 (6) ◽  
pp. 1138-1143 ◽  
Author(s):  
Shiro Itagaki ◽  
Vadivel Ganapathy ◽  
Horace T. B. Ho ◽  
Mingyan Zhou ◽  
Ellappan Babu ◽  
...  

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