Interspecies Comparison of the Functional Characteristics of Plasma Membrane Monoamine Transporter (PMAT) Between Human, Rat and Mouse

Overview

Journal J Chem Neuroanat

Specialties Anatomy & Histology
Chemistry
Neurology

Date 2016 Sep 20

PMID 27641077

Citations 12

Authors

Yoshiyuki Shirasaka

Nora Lee

Haichuan Duan

Horace Ho

Joanna Pak

Joanne Wang

Affiliations

Soon will be listed here.

Abstract

Plasma membrane monoamine transporter (PMAT) is a newly discovered monoamine transporter belonging to the equilibrative nucleoside transporter family. Highly expressed in the brain, PMAT represents a major uptake transporter that may play a role in monoamine clearance. Although human PMAT has been functionally characterized at the molecular level, rodent models are often used to evaluate PMAT function in ex vivo and in vivo studies. The aim of this study was to examine if there is potential species difference in the functional characteristics of PMAT between human, rat and mouse. A set of transfected cells stably expressing human PMAT (MDCK/hPMAT), rat Pmat (MDCK/rPmat) and mouse Pmat (Flp293/mPmat) were constructed. In MDCK/hPMAT, MDCK/rPmat and Flp293/mPmat cells, cellular localization analyses revealed that hPMAT, rPmat and mPmat are expressed and mainly localized to the plasma membranes of cells. The uptake of MPP, serotonin and dopamine by MDCK/hPMAT, MDCK/rPmat and Flp293/mPmat cells was significantly increased compared with those by the mock transfection control. In contrast, two nucleosides, uridine and adenosine, minimally interacted with PMAT/Pmat in all species. The hPMAT-, rPmat- and mPmat-mediated uptakes of MPP, serotonin and dopamine were saturable, with K values of 33.7μM, 70.2μM and 49.5μM (MPP), 116μM, 82.9μM and 231μM (serotonin), and 201μM, 271μM and 466μM (dopamine), respectively, suggesting similar substrate affinities between human and rodent PMAT/Pmat. The prototypical inhibitors, decynium 22 and GBR12935, also showed similar inhibition potencies between species. In conclusion, the present study demonstrated interspecies similarities in the functional characteristics of human and rodent PMAT/Pmat, which indicate a practical utility of rat and mouse animal models for further investigating and extrapolating the in vivo function of PMAT in humans.

Citing Articles

Dopamine internalization via Uptake and stimulation of intracellular D-receptor-dependent calcium mobilization and CDP-diacylglycerol signaling.

Kang W, Siewe A, Oluigbo C, Arijesudade M, Brailoiu E, Undieh A Front Pharmacol. 2024; 15:1422998.

PMID: 39525629 PMC: 11543475. DOI: 10.3389/fphar.2024.1422998.

Kinetic Properties and Pharmacological Modulation of High- and Low-Affinity Dopamine Transport in Striatal Astrocytes of Adult Rats.

Socan V, Dolinar K, Krzan M Int J Mol Sci. 2024; 25(10).

PMID: 38791173 PMC: 11121484. DOI: 10.3390/ijms25105135.

Organic cation transporters in psychiatric and substance use disorders.

Honan L, Fraser-Spears R, Daws L Pharmacol Ther. 2023; 253:108574.

PMID: 38072333 PMC: 11052553. DOI: 10.1016/j.pharmthera.2023.108574.

Species Differences in Tryptophan Metabolism and Disposition.

Badawy A, Guillemin G Int J Tryptophan Res. 2022; 15:11786469221122511.

PMID: 36325027 PMC: 9620070. DOI: 10.1177/11786469221122511.

Uncovering Functional Contributions of PMAT () to Monoamine Clearance Using Pharmacobehavioral Tools.

Beaver J, Weber B, Ford M, Anello A, Kassis S, Gilman T Cells. 2022; 11(12).

PMID: 35741002 PMC: 9220966. DOI: 10.3390/cells11121874.

References

. Management of diabetes from preconception to the postnatal period: summary of NICE guidance. BMJ. 2008; 336(7646):714-7. PMC: 2276266. DOI: 10.1136/bmj.39505.641273.AD. View

Sweet D, Pritchard J . rOCT2 is a basolateral potential-driven carrier, not an organic cation/proton exchanger. Am J Physiol. 1999; 277(6):F890-8. DOI: 10.1152/ajprenal.1999.277.6.F890. View

Dahlin A, Xia L, Kong W, Hevner R, Wang J . Expression and immunolocalization of the plasma membrane monoamine transporter in the brain. Neuroscience. 2007; 146(3):1193-211. PMC: 2683847. DOI: 10.1016/j.neuroscience.2007.01.072. View

Zhou M, Xia L, Engel K, Wang J . Molecular determinants of substrate selectivity of a novel organic cation transporter (PMAT) in the SLC29 family. J Biol Chem. 2006; 282(5):3188-95. PMC: 2672960. DOI: 10.1074/jbc.M609421200. View

Zhou M, Duan H, Engel K, Xia L, Wang J . Adenosine transport by plasma membrane monoamine transporter: reinvestigation and comparison with organic cations. Drug Metab Dispos. 2010; 38(10):1798-805. PMC: 2957165. DOI: 10.1124/dmd.110.032987. View

Okura T, Kato S, Takano Y, Sato T, Yamashita A, Morimoto R . Functional characterization of rat plasma membrane monoamine transporter in the blood-brain and blood-cerebrospinal fluid barriers. J Pharm Sci. 2011; 100(9):3924-38. DOI: 10.1002/jps.22594. View

Nakamichi N, Shima H, Asano S, Ishimoto T, Sugiura T, Matsubara K . Involvement of carnitine/organic cation transporter OCTN1/SLC22A4 in gastrointestinal absorption of metformin. J Pharm Sci. 2013; 102(9):3407-17. DOI: 10.1002/jps.23595. View

Wright S, Dantzler W . Molecular and cellular physiology of renal organic cation and anion transport. Physiol Rev. 2004; 84(3):987-1049. DOI: 10.1152/physrev.00040.2003. View

Duan H, Wang J . Selective transport of monoamine neurotransmitters by human plasma membrane monoamine transporter and organic cation transporter 3. J Pharmacol Exp Ther. 2010; 335(3):743-53. PMC: 2993547. DOI: 10.1124/jpet.110.170142. View

10.

Koepsell H, Lips K, Volk C . Polyspecific organic cation transporters: structure, function, physiological roles, and biopharmaceutical implications. Pharm Res. 2007; 24(7):1227-51. DOI: 10.1007/s11095-007-9254-z. View

11.

Koepsell H, Schmitt B, Gorboulev V . Organic cation transporters. Rev Physiol Biochem Pharmacol. 2003; 150:36-90. DOI: 10.1007/s10254-003-0017-x. View

12.

Yamaoka K, Tanigawara Y, Nakagawa T, Uno T . A pharmacokinetic analysis program (multi) for microcomputer. J Pharmacobiodyn. 1981; 4(11):879-85. DOI: 10.1248/bpb1978.4.879. View

13.

Barnes K, Dobrzynski H, Foppolo S, Beal P, Ismat F, Scullion E . Distribution and functional characterization of equilibrative nucleoside transporter-4, a novel cardiac adenosine transporter activated at acidic pH. Circ Res. 2006; 99(5):510-9. DOI: 10.1161/01.RES.0000238359.18495.42. View

14.

Xia L, Engel K, Zhou M, Wang J . Membrane localization and pH-dependent transport of a newly cloned organic cation transporter (PMAT) in kidney cells. Am J Physiol Renal Physiol. 2006; 292(2):F682-90. PMC: 2672957. DOI: 10.1152/ajprenal.00302.2006. View

15.

Engel K, Zhou M, Wang J . Identification and characterization of a novel monoamine transporter in the human brain. J Biol Chem. 2004; 279(48):50042-9. DOI: 10.1074/jbc.M407913200. View

16.

Ho H, Wang J . Tyrosine 112 is essential for organic cation transport by the plasma membrane monoamine transporter. Biochemistry. 2010; 49(36):7839-46. PMC: 2995015. DOI: 10.1021/bi100560q. View

17.

Baldwin S, Yao S, Hyde R, Ng A, Foppolo S, Barnes K . Functional characterization of novel human and mouse equilibrative nucleoside transporters (hENT3 and mENT3) located in intracellular membranes. J Biol Chem. 2005; 280(16):15880-7. DOI: 10.1074/jbc.M414337200. View

18.

Duan H, Wang J . Impaired monoamine and organic cation uptake in choroid plexus in mice with targeted disruption of the plasma membrane monoamine transporter (Slc29a4) gene. J Biol Chem. 2012; 288(5):3535-44. PMC: 3561572. DOI: 10.1074/jbc.M112.436972. View

19.

Engel K, Wang J . Interaction of organic cations with a newly identified plasma membrane monoamine transporter. Mol Pharmacol. 2005; 68(5):1397-407. DOI: 10.1124/mol.105.016832. View

20.

Zhou M, Xia L, Wang J . Metformin transport by a newly cloned proton-stimulated organic cation transporter (plasma membrane monoamine transporter) expressed in human intestine. Drug Metab Dispos. 2007; 35(10):1956-62. PMC: 2672958. DOI: 10.1124/dmd.107.015495. View