RT Journal Article
SR Electronic
T1 β-Phenylethylamine Alters Monoamine Transporter Function via Trace Amine-Associated Receptor 1: Implication for Modulatory Roles of Trace Amines in Brain
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 617
OP 628
DO 10.1124/jpet.107.134247
VO 325
IS 2
A1 Zhihua Xie
A1 Gregory M. Miller
YR 2008
UL http://jpet.aspetjournals.org/content/325/2/617.abstract
AB Brain monoamines include common biogenic amines (dopamine, norepinephrine, and serotonin) and trace amines [β-phenylethylamine (β-PEA), tyramine, tryptamine, and octopamine]. Common biogenic amines are well established as neurotransmitters, but the roles and functional importance of trace amines remain elusive. Here, we re-evaluated the interaction of trace amines with trace amine-associated receptor 1 (TAAR1) and investigated effects of β-PEA on monoamine transporter function and influence of monoamine autoreceptors on TAAR1 signaling. We confirmed that TAAR1 was activated by trace amines and demonstrated that TAAR1 activation by β-PEA significantly inhibited uptake and induced efflux of [3H]dopamine, [3H]norepinephrine, and [3H]serotonin in transfected cells. In brain synaptosomes, β-PEA significantly inhibited uptake and induced efflux of [3H]dopamine and [3H]serotonin in striatal and [3H]norepinephrine in thalamic synaptosomes of rhesus monkeys and wild-type mice, but it lacked the same effects in synaptosomes of TAAR1 knockout mice. The effect of β-PEA on efflux was blocked by transporter inhibitors in either the transfected cells or wild-type mouse synaptosomes. We also demonstrated that TAAR1 signaling was not affected by monoamine autoreceptors at exposure to trace amines that we show to have poor binding affinity for the autoreceptors relative to common biogenic amines. These results reveal that β-PEA alters monoamine transporter function via interacting with TAAR1 but not monoamine autoreceptors. The functional profile of β-PEA may reveal a common mechanism by which trace amines exert modulatory effects on monoamine transporters in brain. The American Society for Pharmacology and Experimental Therapeutics