In vitro toxicity of the galanin receptor 3 antagonist SNAP 37889.

Abstract

Galanin and its receptors (GAL1, GAL2, GAL3) modulate a range of neuronal, immune and vascular activities. In vivo administration of SNAP 37889 (1-phenyl-3-[[3-(trifluoromethyl)phenyl]imino]-1H-indol-2-one), a potent small non-peptidergic antagonist of GAL3, was reported to reduce anxiety- and depression-related behavior, ethanol consumption, and antagonizes the effect of galanin on plasma extravasation in rodent models. Accordingly, SNAP 37889 has been proposed as a potential therapeutic agent to treat anxiety and depression disorders. Therefore, we evaluated the toxicity of SNAP 37889 to different cell types. Our experiments revealed that SNAP 37889 (≥10μM) induced apoptosis in epithelial (HMCB) and microglial (BV-2) cell lines expressing endogenous GAL3, in peripheral blood mononuclear cells and promyelocytic leukemia cells (HL-60) expressing GAL2, and in a neuronal cell line (SH-SY5Y) lacking galanin receptor expression altogether. In conclusion, SNAP 37889 is toxic to a variety of cell types independent of GAL3 expression. We caution that the clinical use of SNAP 37889 at doses that might be used to treat anxiety- or depression- related diseases could have unexpected non-galanin receptor-mediated toxicity, especially on immune cells.

• Authors: Andreas Koller, Raphaela Rid, Marlena Beyreis, Rodolfo Bianchini, Barbara S Holub, Andreas Lang, Felix Sternberg, Bernhard Brodowicz, Ognjen Velickovic, Martin Jakab, Hubert Kerschbaum, Kamil Önder, Barbara Kofler
• Journal: Neuropeptides (Neuropeptides) Vol. 56 Pg. 83-8 (04 2016) ISSN: 1532-2785 [Electronic] Netherlands
• PMID: 26725588 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Ltd. All rights reserved.

Chemical References

• 1-phenyl-3-((3-(trifluoromethyl)phenyl)imino)-1H-indol-2-one
• Indoles
• Receptor, Galanin, Type 3

Topics

• Animals
• Apoptosis (drug effects)
• Cell Line
• Cell Line, Tumor
• Cell Survival (drug effects)
• Epithelial Cells (drug effects)
• Humans
• In Vitro Techniques
• Indoles (toxicity)
• Leukocytes, Mononuclear (drug effects)
• Mice
• Microglia (drug effects)
• Neurons (drug effects)
• Receptor, Galanin, Type 3 (antagonists & inhibitors)