학술논문
The Tunicate Metabolite 2-(3,5-Diiodo-4-methoxyphenyl)ethan-1-amine Targets Ion Channels of Vertebrate Sensory Neurons
Document Type
Article
Author
Paguigan, Noemi D.; Yan, Yannan; Karthikeyan, Manju; Chase, Kevin; Carter, Jackson; Leavitt, Lee S.; Lim, Albebson L.; Lin, Zhenjian; Memon, Tosifa; Christensen, Sean; Bentzen, Bo H.; Schmitt, Nicole; Reilly, Christopher A.; Teichert, Russell W.; Raghuraman, Shrinivasan; Olivera, Baldomero M.; Schmidt, Eric W.
Source
ACS Chemical Biology; September 2021, Vol. 16 Issue: 9 p1654-1662, 9p
Subject
Language
ISSN
15548929; 15548937
Abstract
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 Xenopusoocytes, 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+]iof 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.