OCT2 and MATE1 provide bidirectional agmatine transport

Agmatine is a biogenic amine (L-arginine metabolite) of potential relevance to several central nervous system (CNS) conditions. The identities of transporters underlying agmatine and polyamine disposition in mammalian systems are not well-defined. The SLC-family organic cation transporters (OCT) OCT1 and OCT2 and multidrug and toxin extrusion transporter-1 (MATE1) are transport systems that may be of importance for the cellular disposition of agmatine and putrescine. We investigated the transport of [³H]agmatine and [ ³H]putrescine in human embryonic kidney (HEK293) cells stably transfected with hOCT1, hOCT2, and hMATE1. Agmatine transport by hOCT1 and hOCT2 was concentration-dependent, whereas only hOCT2 demonstrated pH-dependent transport. hOCT2 exhibited a greater affinity for agmatine (K _m=1.84±0.38 mM) than did hOCT1 (K_m=18.73±4. 86 mM). Putrescine accumulation was pHand concentration-dependent in hOCT2-HEK cells (K_m=11.29±4.26 mM) but not hOCT1- HEK cells. Agmatine accumulation, in contrast to putrescine, was significantly enhanced by hMATE1 overexpression, and was saturable (K_m=240±31 μM; V _max=192±10 pmol/min/mg of protein). Intracellular agmatine was also trans-stimulated (effluxed) from hMATE1-HEK cells in the presence of an inward proton-gradient. The hMATE1-mediated transport of agmatine was inhibited by polyamines, the prototypical substrates MPP+ and paraquat, as well as guanidine and arcaine, but not L-arginine. These results suggest that agmatine disposition may be influenced by hOCT2 and hMATE1, two transporters critical in the renal elimination of xenobiotic compounds.