Activation of TRPM3 by a potent synthetic ligand reveals a role in peptide release

Held K, Kichko T, De Clercq K, Klaassen H, Van Bree R, Vanherck JC, Marchand A, Reeh P, Chaltin P, Voets T, Vriens J (2015)

Publication Type: Journal article

Publication year: 2015

Journal

Proceedings of the National Academy of Sciences of the United States of America National Academy of Sciences

Book Volume: 112

Pages Range: E1363-72

Journal Issue: 11

DOI: 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.

Authors with CRIS profile

Tetyana Kichko Lehrstuhl für Physiologie Peter Reeh Professur für Physiologie

Involved external institutions

Katholieke Universiteit Leuven (KUL) / Catholic University of Leuven BE Belgium (BE) Center for Innovation and Stimulation of Drug Discovery (CISTIM) BE Belgium (BE)

How to cite

APA:

Held, K., Kichko, T., De Clercq, K., Klaassen, H., Van Bree, R., Vanherck, J.-C.,... Vriens, J. (2015). Activation of TRPM3 by a potent synthetic ligand reveals a role in peptide release. Proceedings of the National Academy of Sciences of the United States of America, 112(11), E1363-72. https://doi.org/10.1073/pnas.1419845112

MLA:

Held, Katharina, et al. "Activation of TRPM3 by a potent synthetic ligand reveals a role in peptide release." Proceedings of the National Academy of Sciences of the United States of America 112.11 (2015): E1363-72.

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