In vitro toxicity of the galanin receptor 3 antagonist SNAP 37889

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

doi:10.1016/j.npep.2015.12.003

In vitro toxicity of the galanin receptor 3 antagonist SNAP 37889

Neuropeptides. 2016 Apr:56:83-8. doi: 10.1016/j.npep.2015.12.003. Epub 2015 Dec 8.

Affiliations

¹ Laura Bassi Centre of Expertise THERAPEP, Research Program for Receptor Biochemistry and Tumor Metabolism, Department of Pediatrics, Paracelsus Medical University, Müllner Hauptstraße 48, 5020 Salzburg, Austria.
² Division of Molecular Dermatology, Department of Dermatology, Paracelsus Medical University, Müllner Hauptstraße 48, 5020 Salzburg, Austria.
³ Department of Cell Biology, University of Salzburg, Hellbrunnerstraße 34, 5020 Salzburg, Austria; Institute of Physiology and Pathophysiology, Paracelsus Medical University, Strubergasse 21, 5020 Salzburg, Austria; Gastein Research Institute, Paracelsus Medical University, Strubergasse 21, 5020 Salzburg, Austria.
⁴ Institute of Physiology and Pathophysiology, Paracelsus Medical University, Strubergasse 21, 5020 Salzburg, Austria.
⁵ Department of Cell Biology, University of Salzburg, Hellbrunnerstraße 34, 5020 Salzburg, Austria.
⁶ Division of Molecular Dermatology, Department of Dermatology, Paracelsus Medical University, Müllner Hauptstraße 48, 5020 Salzburg, Austria; Procomcure Biotech GmbH, Austria.
⁷ Laura Bassi Centre of Expertise THERAPEP, Research Program for Receptor Biochemistry and Tumor Metabolism, Department of Pediatrics, Paracelsus Medical University, Müllner Hauptstraße 48, 5020 Salzburg, Austria. Electronic address: B.Kofler@salk.at.

PMID: 26725588
DOI: 10.1016/j.npep.2015.12.003

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.

Keywords: Anxiety; Cytotoxicity; Depression; Galanin; Galanin receptor 3; SNAP 37889.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

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*

Substances

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