Distribution of exogenous [125I]-3-iodothyronamine in mouse in vivo: relationship with trace amine-associated receptors

Abstract

3-Iodothyronamine (T 1 AM) is a novel chemical messenger, structurally related to thyroid hormone, able to interact with G protein-coupled receptors known as trace amine-associated receptors (TAARs). Little is known about the physiological role of T 1 AM. In this prospective, we synthesized 125 I]-T 1 AM was taken up by each organ. A significant increase in tissue vs blood concentration occurred in gallbladder, stomach, intestine, liver, and kidney. Tissue radioactivity decreased exponentially over time, consistent with biliary and urinary excretion, and after 24 h, 75% of the residual radioactivity was detected in liver, muscle, and adipose tissue. TAARs were expressed only at trace amounts in most of the tissues, the exceptions being TAAR1 in stomach and testis and TAAR8 in intestine, spleen, and testis. Thus, while T 1 AM has a systemic distribution, TAARs are only expressed in certain tissues suggesting that other high-affinity molecular targets besides TAARs exist.

In the brain of mice, 3-iodothyronamine (T1AM) is converted into 3-iodothyroacetic acid (TA1) and it is included within the signaling network connecting thyroid hormone metabolites with histamine

“…Subsequently, additional molecular targets were tentatively identified, including alpha-2 receptors (Regard et al, 2007). Whether the behavioral effects of T1AM result from the activation of such receptors remains to be demonstrated (Chiellini et al, 2012;Panas et al, 2010).…”

3-Iodothyronamine: A High Potency Metabolic Hormone and its Potential for Therapeutic Applications

“…This suggests that TAAR, or at least TAAR1, agonist activation is not necessary for at least some of the metabolic responses due to T1AM. Radioactive tracing of exogenous 125 I labeled-T1AM did not indicate any direct relationship with TAAR receptor expression across 8 different TAAR isoforms and measured radioactivity in tissues [23]. Additionally, it was found that expression of TAARs in mice and rat proved to be very low in most tissues; TAAR gene expression was only detected in trace amounts across most tissues, with notable expression levels of TAAR1 in the stomach and testis, and TAAR8 in the testis, intestine, and spleen [23].…”

“…Distribution of measured radioactivity in response to acute 125 I labeled-T1AM injection in mice indicated abundant levels of accumulation in stomach, intestine, kidney, and gallbladder within as little as 30 minutes [23]; however, this is thought to reflect excretion pattern of excess T1AM rather than functional activity sites. Elevated radiation levels in liver, fat, and skeletal muscle for a full 24 hours after 125 I labeled-T1AM injection provides evidence for these tissues as possible storage sites of T1AM [23].…”

“…Distribution of measured radioactivity in response to acute 125 I labeled-T1AM injection in mice indicated abundant levels of accumulation in stomach, intestine, kidney, and gallbladder within as little as 30 minutes [23]; however, this is thought to reflect excretion pattern of excess T1AM rather than functional activity sites. Elevated radiation levels in liver, fat, and skeletal muscle for a full 24 hours after 125 I labeled-T1AM injection provides evidence for these tissues as possible storage sites of T1AM [23]. Initial detection methods of using LC/ MS revealed very low circulating levels of T1AM around 0.3 nM range [15], however, an anti-body based assay detention method measured circulating T1AM levels in human at approximately 66 nM [14] which approaches levels of circulating T4 (70-150 nM) and those concentrations of T1AM recorded in other tissues [15].…”

“…Originally discovered in rat brain [1], T1AM has been detected in a wide panel of tissues [15,23], and is present in plasma [14,25] which is likely the primary means of delivery to target tissues. Distribution of measured radioactivity in response to acute 125 I labeled-T1AM injection in mice indicated abundant levels of accumulation in stomach, intestine, kidney, and gallbladder within as little as 30 minutes [23]; however, this is thought to reflect excretion pattern of excess T1AM rather than functional activity sites.…”