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Example:10.1021/acsami.1c06204 or Chem. Rev., 2007, 107, 2411-2502
The Tunicate Metabolite 2-(3,5-Diiodo-4-methoxyphenyl)ethan-1-amine Targets Ion Channels of Vertebrate Sensory Neurons
ACS Chemical Biology  (IF5.1),  Pub Date : 2021-08-23, DOI: 10.1021/acschembio.1c00328
Noemi D. Paguigan, Yannan Yan, Manju Karthikeyan, Kevin Chase, Jackson Carter, Lee S. Leavitt, Albebson L. Lim, Zhenjian Lin, Tosifa Memon, Sean Christensen, Bo H. Bentzen, Nicole Schmitt, Christopher A. Reilly, Russell W. Teichert, Shrinivasan Raghuraman, Baldomero M. Olivera, Eric W. Schmidt

Marine tunicates produce defensive amino-acid-derived metabolites, including 2-(3,5-diiodo-4-methoxyphenyl)ethan-1-amine (DIMTA), but their mechanisms of action are rarely known. Using an assay-guided approach, we found that out of the many different sensory cells in the mouse dorsal root ganglion (DRG), DIMTA selectively affected low-threshold cold thermosensors. Whole-cell electrophysiology experiments using DRG cells, channels expressed in Xenopus oocytes, and human cell lines revealed that DIMTA blocks several potassium channels, reducing the magnitude of the afterhyperpolarization and increasing the baseline intracellular calcium concentration [Ca2+]i of low-threshold cold thermosensors. When injected into mice, DIMTA increased the threshold of cold sensation by >3 °C. DIMTA may thus serve as a lead in the further design of compounds that inhibit problems in the cold-sensory system, such as cold allodynia and other neuropathic pain conditions.