Pharmacological characterization of a high-affinity p-tyramine transporter in rat brain synaptosomes

• Published in: Scientific reports Vol. 6; no. 1; p. 38006
• Main Authors: Berry, Mark D, Hart, Shannon, Pryor, Anthony R, Hunter, Samantha, Gardiner, Danielle
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 30.11.2016
• Subjects: Affinity; Amines; Animals; Biological Transport, Active - physiology; Cortex; Dopamine transporter; Exocytosis; Lipid bilayers; Localization; Male; Monoamines; Neostriatum; Norepinephrine; Oct-2 protein; Organic cation transporter; Organic Cation Transporter 2 - metabolism; Presynaptic Terminals - metabolism; Rats; Rats, Wistar; Receptors, G-Protein-Coupled - metabolism; Rodents; Synaptosomes; Synaptosomes - metabolism; Tyramine; Tyramine - metabolism
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep38006

p-Tyramine is an archetypal member of the endogenous family of monoamines known as trace amines, and is one of the endogenous agonists for trace amine-associated receptor (TAAR)1. While much work has focused on the function of TAAR1, very little is known about the regulation of the endogenous agonists. We have previously reported that p-tyramine readily crosses lipid bilayers and that its release from synaptosomes is non-exocytotic. Such release, however, showed characteristics of modification by one or more transporters. Here we provide the first characterization of such a transporter. Using frontal cortical and striatal synaptosomes we show that p-tyramine passage across synaptosome membranes is not modified by selective inhibition of either the dopamine, noradrenaline or 5-HT transporters. In contrast, inhibition of uptake-2 transporters significantly slowed p-tyramine re-uptake. Using inhibitors of varying selectivity, we identify Organic Cation Transporter 2 (OCT2; SLC22A2) as mediating high affinity uptake of p-tyramine at physiologically relevant concentrations. Further, we confirm the presence of OCT2 protein in synaptosomes. These results provide the first identification of a high affinity neuronal transporter for p-tyramine, and also confirm the recently described localization of OCT2 in pre-synaptic terminals.