Endocrine Abstracts

3-Iodothyronamine (3-T₁AM) is an endogenous metabolite of thyroid hormone (TH) for which was shown to have various effects. One of the effects is body temperature decline, which may be related with menthol receptor TRPM8. Normally, this ion channel is expressed in neuronal tissue, where it has a nociceptive role. Functional TRPM8 expression has also been shown in non-neuronal cells of the eye such as corneal and conjunctival epithelial cells, corneal endothelial cells as well as human corneal keratocytes. Furthermore, we could demonstrate in previous studies that 3-T₁AM acts as a cooling agent in human corneal epithelial and conjunctival epithelial cells and that it is suppressing TRPV1 channel (capsaicin receptor), which plays an important role in dry eye disease. Here, we determined in a human corneal endothelial cell line (HCEC-12) and a human corneal keratocyte cell line (HCK) if 3-T₁AM also acts as a cooling agent to directly affect TRPM8 at a constant temperature. Functional activity was evaluated by comparing the effects of 3-T₁AM with those of TRPM8 known agonists on intracellular Ca²⁺ currents and whole-cell currents using fluorescent Ca²⁺-imaging and planar patch-clamping. Menthol (500 μM), a specific TRPM8 activator, evoked a Ca²⁺ influx as well as an increase of whole-cell currents. This effect could be blocked by BCTC (20 μM) and AMTB (20 μM), both selective TRPM8 antagonists. Notably, comparable effects were observed with 1 μM 3-T₁AM. Overall, this study completes our previous studies of human corneal and conjunctival epithelial cells. Interestingly, the effect of 3-T₁AM has a similar Ca²⁺ response pattern and similar whole-cell current pattern in all three layers of the cornea. Therefore, this might represent a general biological phenomenon. Further investigation of 3-T₁AM effects on the cornea should be performed in order to better characterize a potential benefit of 3-T₁AM on the treatment of dry eye disease.