Are organic cation transporters capable of transporting prostaglandins?

Abstract

The non-neuronal monoamine transporters OCT1, OCT2 and EMT (human gene symbols SLC22A1-A3) efficiently transport a number of positively-charged monoamines and some small organic cations across the plasma membrane, and thus are implicated in the inactivation of released monoamine transmitters (e.g. noradrenaline, histamine, agmatine) in vivo. Although prostaglandins are full anions at physiological pH, data from a recent publication suggest efficient transport of the prostaglandins PGE₂ and ${\text{PGF}}_{{{\text{2 $\alpha $ }}}}$ by OCT1 and OCT2. In the present study we have reexamined transport of PGE₂ by OCT2 from human (OCT2h). Uptake of substrate into monolayers of 293 cells, stably transfected to express OCT2h, was compared to uptake into non-transfected control cells. Efficiency of transport of the established substrate ³H-1-methyl-4-phenylpyridinium (MPP⁺), expressed as clearance, was high at 81 μl min⁻¹ mg protein⁻¹ on average. By contrast, uptake of ³H-PGE₂ was virtually identical for control cells and OCT2h cells. The efficiency of transport was 0.1±0.6, 1.0±0.3, and 0.7±0.4 μl min⁻¹ mg protein⁻¹ for cell lysis with methanol, HClO₄, and Triton X-100 respectively. Similar results were obtained with unlabeled MPP⁺ (192±12 μl min⁻¹ mg protein⁻¹) and PGE₂ (0.3±0.1 μl min⁻¹ mg protein⁻¹) in LC-MS/MS analysis. We conclude that OCT2h is not capable of transporting prostaglandins. The data from the previous report may represent binding rather than transport. Our comparison of transport efficiencies confirms the notion that relevant substrates of OCT1, OCT2, and EMT must carry a positive charge.