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Updated: Jun 6, 2026
13:16
Characterization of Membrane Transporters by Heterologous Expression in E. coli and Production of Membrane Vesicles
Published on: December 31, 2019
OCT2 and MATE1 provide bidirectional agmatine transport
Tate N Winter1, William F Elmquist, Carolyn A Fairbanks
1Departments of Pharmaceutics, Pharmacology, and Neuroscience, University of Minnesota, Minneapolis, Minnesota 55455, USA.
Molecular Pharmaceutics
|December 7, 2010
Summary
Agmatine transport in the body is clarified by identifying key transporters. Organic cation transporters 1 and 2 (OCT1, OCT2) and multidrug and toxin extrusion 1 (MATE1) influence agmatine disposition, particularly in the kidneys.
Area of Science:
- Pharmacology and Toxicology
- Molecular Biology
- Biochemistry
Background:
- Agmatine, a biogenic amine and l-arginine metabolite, has potential implications for central nervous system (CNS) disorders.
- The specific transporters responsible for agmatine and polyamine uptake and elimination in mammals are not fully understood.
- Organic cation transporters (OCT1, OCT2) and multidrug and toxin extrusion 1 (MATE1) are candidate transporters for agmatine and putrescine.
Purpose of the Study:
- To investigate the role of human organic cation transporters (hOCT1, hOCT2) and multidrug and toxin extrusion 1 (hMATE1) in agmatine and putrescine transport.
- To characterize the kinetic and regulatory properties of agmatine and putrescine transport mediated by these transporters.
Main Methods:
- Transport assays using radiolabeled [(3)H]agmatine and [(3)H]putrescine in human embryonic kidney (HEK293) cells stably expressing hOCT1, hOCT2, or hMATE1.
- Analysis of concentration-dependent, pH-dependent, and trans-stimulation effects on transporter activity.
- Determination of kinetic parameters (K(m), V(max)) and substrate inhibition profiles.
Main Results:
- Agmatine transport was concentration-dependent for both hOCT1 and hOCT2, with hOCT2 showing higher affinity (K(m) = 1.84 mM) than hOCT1 (K(m) = 18.73 mM).
- Putrescine transport was pH- and concentration-dependent in hOCT2-HEK cells but not hOCT1-HEK cells.
- hMATE1 significantly enhanced agmatine accumulation in a saturable manner (K(m) = 240 μM) and mediated agmatine efflux via a proton gradient. Agmatine transport by hMATE1 was inhibited by polyamines, MPP+, paraquat, guanidine, and arcaine, but not l-arginine.
Conclusions:
- Human OCT2 and MATE1 are key transporters involved in the cellular disposition and potential renal elimination of agmatine.
- These findings provide crucial insights into the mechanisms governing agmatine homeostasis and its relevance in CNS conditions and xenobiotic handling.
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