Introduction: 3-Iodothyronamine (T1AM) is a novel endogenous relative of thyroid hormone able to interact with specific G protein-coupled receptors, known as trace amine-associated receptors (TAAR). Metabolic, endocrine and cardiac effects of exogenous T1AM have been reported.
Methods: We synthesized radiolabelled T1AM, [125I]-T1AM, and explored its distribution in different mouse organs after injection in the tail vein. The specificity of [125I]-T1AM was checked in parallel experiments, in which a 100-fold excess of unlabeled T1AM was injected 5 min before the radioligand. We also performed an in vivo evaluation of TAAR expression by quantitative real-time PCR, using specific primers for the nine known TAAR subtypes.
Results: [125I]-T1AM preferentially distributed to the gastrointestinal tract, liver and kidney: in particular at 30 min the highest levels of radioactivity (expressed as percentage of injected dose per g wet weight) were detected in gallbladder, stomach, intestine, liver and kidney (23.3, 8.6, 7.4, 6.1 and 7.2 respectively) and at 60 min top values were still present in gallbladder, liver and kidney (14.7, 6.1 and 6.5 respectively). At 24 h however the highest residual concentration was detecetd in liver and adipose tissue (1.2 and 0.5 respectively). TAAR expression investigations showed that in most tissues TAARs were expressed only at trace amounts (<10 copies per μg mRNA). Higher expression was detecetd in stomach and testis for TAAR1 (83 and 55 copies per μg mRNA) and in small bowel, spleen and testis for TAAR8 (16, 19 and 12 copies per microg mRNA). Notably, TAAR expression was negligible in liver and kidney.
Conclusions: Exogenous [125I]-T1AM is preferentially taken up by the liver, kidney and gastrointestinal tract. TAAR binding seems unable to account for T1AM distribution suggesting that T1AM binds to different targets, particularly in liver and kidney.