Abstract
The decarboxylated and deiodinated thyroid hormone (TH) derivative, 3-iodothyronamine (3-T1AM), is suggested to be involved in energy metabolism and thermoregulation. G protein-coupled receptors (GPCRs) are known as the main targets for 3-T1AM; however, transient receptor potential channels (TRPs) were also recently identified as new targets of 3-T1AM. This article reviews the current knowledge of a putative novel role of 3-T1AM in the modulation of TRPs. Specifically, the TRP melastatin 8 (TRPM8) was identified as a target of 3-T1AM in different cell types including neoplastic cells, whereby 3-T1AM significantly increased cytosolic Ca2+ through TRPM8 activation. Similarly, the β-adrenergic receptor is involved in 3-T1AM-induced Ca2+ influx. Therefore, it has been suggested that 3-T1AM-induced Ca2+ mobilization might be due to β-adrenergic receptor/TRPM8 channel interaction, which adds to the complexity of GPCR regulation by TRPs. It has been revealed that TRPM8 activation leads to a decline in TRPV1 activity, which may be of therapeutic benefit in clinical circumstances such as treatment of TRPV1-mediated inflammatory hyperalgesia, colitis, and dry eye syndrome. This review also summarizes the inverse association between changes in TRPM8 and TRPV1 activity after 3-T1AM stimulation. This finding prompted further detailed investigations of the interplay between 3-T1AM and the GPCR/TRPM8 axis and indicated the probability of additional GPCR/TRP constellations that are modulated by this TH derivative.
Highlights
Thyronamines (TAMs) are identified as a novel class of endogenous signaling compounds
Administration of 3-T1AM in mice resulted in concentration-dependent reversible effects on body temperature, energy metabolism, and cardiac and neurological functions compared with vehicle-treated controls [1]
The overall aim of this review is to summarize the modulation of transient receptor potential channels (TRPs) through 3-T1AM
Summary
Thyronamines (TAMs) are identified as a novel class of endogenous signaling compounds. Two representatives of TAMs, known as 3-iodothyronamine (3-T1AM) and thyronamine (T0AM), have been identified in vivo. Both compounds were detected in blood, heart, brain, thyroid, and many other tissues in rodents [1]. Endogenous TAM concentration may be lower compared to thyroid hormone (TH), it is noteworthy that the tissue-specific and subcellular distributions of TAMs are unknown. The discovery of 3-T1AM and the profound pharmacological effects of this endogenous signaling compound have raised interest to elucidate its signaling properties [1, 3].
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