Nature Medicine
10, 638 - 642 (2004)
Published online: 16 May 2004; | doi:10.1038/nm1051
3-Iodothyronamine is an endogenous and rapid-acting derivative of thyroid hormoneThomas S Scanlan1, Katherine L Suchland2, 7, Matthew E Hart1, 7, Grazia Chiellini3, Yong Huang4, Paul J Kruzich2, Sabina Frascarelli3, Dane A Crossley II2, James R Bunzow2, Simonetta Ronca-Testoni3, Emil T Lin4, Daniel Hatton5, Riccardo Zucchi3
& David K Grandy2, 61
Departments of Pharmaceutical Chemistry and Cellular & Molecular Pharmacology, University of California-San Francisco, San Francisco, California 94143-2280, USA. 2
Department of Physiology & Pharmacology, Oregon Health & Science University, Portland, Oregon 97239-3098, USA. 3
Dipartimento di Scienze dell'Uomo e dell'Ambiente, Sezione di Biochimica, Università di Pisa, via Roma 55, I-56100 Pisa, Italy. 4
Department of Biopharmaceutical Sciences, University of California−San Francisco, San Francisco, California 94143-0446, USA. 5
Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, Oregon 97239-3098, USA. 6
Department of Cell & Developmental Biology, Oregon Health & Science University, Portland, Oregon 97239-3098, USA. 7
These authors contributed equally to this work.
Correspondence should be addressed to Thomas S Scanlan scanlan@cgl.ucsf.edu or David K Grandy grandyd@ohsu.eduThyroxine (T4) is the predominant form of thyroid hormone (TH). Hyperthyroidism, a condition associated with excess TH, is characterized by increases in metabolic rate, core body temperature and cardiac performance. In target tissues, T4 is enzymatically deiodinated to 3,5,3'-triiodothyronine (T3), a high-affinity ligand for the nuclear TH receptors TR and TR , whose activation controls normal vertebrate development and physiology1. T3-modulated transcription of target genes via activation of TR and TR is a slow process, the effects of which manifest over hours and days. Although rapidly occurring effects of TH have been documented, the molecules that mediate these non-genomic effects remain obscure2,
3. Here we report the discovery of 3-iodothyronamine (T1AM), a naturally occurring derivative of TH that in vitro is a potent agonist of the G protein−coupled trace amine receptor TAR1. Administering T1AM in vivo induces profound hypothermia and bradycardia within minutes. T1AM treatment also rapidly reduces cardiac output in an ex vivo working heart preparation. These results suggest the existence of a new signaling pathway, stimulation of which leads to rapid physiological and behavioral consequences that are opposite those associated with excess TH.
MORE ARTICLES LIKE THIS These links to content published by NPG are automatically generated.
|
