Agmatine is efficiently transported by non-neuronal monoamine transporters extraneuronal monoamine transporter (EMT) and organic cation transporter 2 (OCT2).
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Grundemann D, Hahne C, Berkels R, Schomig E
Agmatine is efficiently transported by non-neuronal monoamine transporters extraneuronal monoamine transporter (EMT) and organic cation transporter 2 (OCT2).
J Pharmacol Exp Ther. 2003 Feb;304(2):810-7.
- PubMed ID
- 12538837 [ View in PubMed]
- Abstract
Agmatine has received considerable attention recently. Available evidence suggests that agmatine functions as a neurotransmitter and inhibits, via induction of antizyme, cellular proliferation. Because of its positive charge, agmatine will not appreciably cross cellular membranes by simple diffusion. Indeed, all physiological models require a channel or transporter protein in the plasma membrane to effect inactivation or nonexocytotic release of agmatine. However, a transport mechanism for agmatine has not been identified on a molecular level so far. In the present study, the non-neuronal monoamine transporters, organic cation transporter (OCT) 1, OCT2, and extraneuronal monoamine transporter (EMT) (gene symbols SLC22A1-A3), both from human and rat, were examined, stably expressed in 293 cells, for [(3)H]agmatine transport. Our results indicate that OCT2 and EMT, but not OCT1, efficiently translocate agmatine. The structural homolog putrescine was not accepted as substrate. Uptake of agmatine via EMT and OCT2 was saturable, with K(m) values of 1 to 2 mM. The affinity of OCT1 was 10-fold lower. Carrier-mediated efflux of agmatine was documented in a trans-stimulation experiment. Finally, uptake of agmatine increased dramatically with increasing pH. Thus, only the singly charged species of agmatine is accepted as substrate. In conclusion, both EMT and OCT2 must be considered for the control of agmatine levels in rat and human.
DrugBank Data that Cites this Article
- Drug Transporters
Drug Transporter Kind Organism Pharmacological Action Actions Agmatine Solute carrier family 22 member 1 Protein Humans UnknownSubstrateDetails Agmatine Solute carrier family 22 member 2 Protein Humans UnknownSubstrateDetails Agmatine Solute carrier family 22 member 3 Protein Humans UnknownSubstrateDetails - Polypeptides
Name UniProt ID Solute carrier family 22 member 2 O15244 Details - Binding Properties
Drug Target Property Measurement pH Temperature (°C) Agmatine Solute carrier family 22 member 1 Ki (nM) 24000000 N/A N/A Details