title: Pharmacological characterization of a high-affinity p-tyramine transporter in rat brain synaptosomes.
abstract: 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.
authors.affiliation: Department of Biochemistry, Memorial University of Newfoundland, St. John's, NL, A1B 3X9, Canada.
authors.forename: Mark D
authors.initials: MD
authors.lastname: Berry
authors.affiliation: Department of Biochemistry, Memorial University of Newfoundland, St. John's, NL, A1B 3X9, Canada.
authors.forename: Shannon
authors.initials: S
authors.lastname: Hart
authors.affiliation: Department of Biochemistry, Memorial University of Newfoundland, St. John's, NL, A1B 3X9, Canada.
authors.forename: Anthony R
authors.initials: AR
authors.lastname: Pryor
authors.affiliation: Department of Biochemistry, Memorial University of Newfoundland, St. John's, NL, A1B 3X9, Canada.
authors.forename: Samantha
authors.initials: S
authors.lastname: Hunter
authors.affiliation: Department of Biochemistry, Memorial University of Newfoundland, St. John's, NL, A1B 3X9, Canada.
authors.forename: Danielle
authors.initials: D
authors.lastname: Gardiner
mesh_terms: D000818:Animals; D001693:Biological Transport, Active / Q000502:physiology; D008297:Male; D000075102:Organic Cation Transporter 2 / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D013574:Synaptosomes / Q000378:metabolism*; D014439:Tyramine / Q000378:metabolism*; D000095383:Trace Amine-Associated Receptors
chemical_list: D000075102:Organic Cation Transporter 2; D043562:Receptors, G-Protein-Coupled; D014439:Tyramine; D000095383:Trace Amine-Associated Receptors; C100590:Slc22a2 protein, rat