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Title: Activation of TRPM3 by a potent synthetic ligand reveals a role in peptide release
Authors: Held, Kathi ×
Kichko, Tatjana
De Clercq, Katrien
Klaassen, Hugo
Van Bree, Rieta
Vanherck, Jean-Christophe
Marchand, Arnaud
Reeh, Peter W
Chaltin, Patrick
Voets, Thomas
Vriens, Joris #
Issue Date: Mar-2015
Publisher: National Academy of Sciences
Series Title: Proceedings of the National Academy of Sciences of the United States of America vol:112 issue:11 pages:E1363-72
Article number: 10.1073/pnas.1419845112
Abstract: Transient receptor potential (TRP) cation channel subfamily M member 3 (TRPM3), a member of the TRP channel superfamily, was recently identified as a nociceptor channel in the somatosensory system, where it is involved in the detection of noxious heat; however, owing to the lack of potent and selective agonists, little is known about other potential physiological consequences of the opening of TRPM3. Here we identify and characterize a synthetic TRPM3 activator, CIM0216, whose potency and apparent affinity greatly exceeds that of the canonical TRPM3 agonist, pregnenolone sulfate (PS). In particular, a single application of CIM0216 causes opening of both the central calcium-conducting pore and the alternative cation permeation pathway in a membrane-delimited manner. CIM0216 evoked robust calcium influx in TRPM3-expressing somatosensory neurons, and intradermal injection of the compound induced a TRPM3-dependent nocifensive behavior. Moreover, CIM0216 elicited the release of the peptides calcitonin gene-related peptide (CGRP) from sensory nerve terminals and insulin from isolated pancreatic islets in a TRPM3-dependent manner. These experiments identify CIM0216 as a powerful tool for use in investigating the physiological roles of TRPM3, and indicate that TRPM3 activation in sensory nerve endings can contribute to neurogenic inflammation.
URI: 
ISSN: 0027-8424
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Organ Systems (+)
Intellectual Property
× corresponding author
# (joint) last author

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