Thyronamines inhibit plasma membrane and vesicular monoamine transport.
Thyroid hormone has long been known to have important transcriptional regulatory activities. Recently, however, the presence of endogenous derivatives of thyroid hormone, thyronamines, has been reported in various mammalian tissues. These derivatives have potent in vitro activity with a class of orphan G-protein-coupled receptors, the trace amine-associated receptors, and profound in vivo effects when administered to mice. We report here a novel neuromodulatory role for thyronamines. In synaptosomal preparations and heterologous expression systems, thyronamines act as specific dopamine and norepinephrine reuptake inhibitors. Thyronamines also inhibit the transport of monoamines into synaptic vesicles. These observations expand the nontranscriptional role of thyroid hormone derivatives and may help to explain the pharmacological effects of thyronamines in vivo.
Snead
Aaron N
AN
Graduate Program in Chemistry and Chemical Biology, University of California at San Francisco, San Francisco, California 94143, USA.
Santos
Magda S
MS
Seal
Rebecca P
RP
Miyakawa
Motonori
M
Edwards
Robert H
RH
Scanlan
Thomas S
TS
D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D021381:Protein Transport / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013970:Thyronines / Q000737:chemistry* / Q000502:physiology*; D050493:Vesicular Monoamine Transport Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism*
D013970:Thyronines; D050493:Vesicular Monoamine Transport Proteins