title: 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.affiliation: 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.
authors.forename: Andreas
authors.initials: A
authors.lastname: Koller
authors.affiliation: Division of Molecular Dermatology, Department of Dermatology, Paracelsus Medical University, Müllner Hauptstraße 48, 5020 Salzburg, Austria.
authors.forename: Raphaela
authors.initials: R
authors.lastname: Rid
authors.affiliation: 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.
authors.forename: Marlena
authors.initials: M
authors.lastname: Beyreis
authors.affiliation: 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.
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Bianchini
authors.affiliation: 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.
authors.forename: Barbara S
authors.initials: BS
authors.lastname: Holub
authors.affiliation: 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.
authors.forename: Andreas
authors.initials: A
authors.lastname: Lang
authors.affiliation: 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.
authors.forename: Felix
authors.initials: F
authors.lastname: Sternberg
authors.affiliation: 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.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Brodowicz
authors.affiliation: Division of Molecular Dermatology, Department of Dermatology, Paracelsus Medical University, Müllner Hauptstraße 48, 5020 Salzburg, Austria.
authors.forename: Ognjen
authors.initials: O
authors.lastname: Velickovic
authors.affiliation: Institute of Physiology and Pathophysiology, Paracelsus Medical University, Strubergasse 21, 5020 Salzburg, Austria.
authors.forename: Martin
authors.initials: M
authors.lastname: Jakab
authors.affiliation: Department of Cell Biology, University of Salzburg, Hellbrunnerstraße 34, 5020 Salzburg, Austria.
authors.forename: Hubert
authors.initials: H
authors.lastname: Kerschbaum
authors.affiliation: Division of Molecular Dermatology, Department of Dermatology, Paracelsus Medical University, Müllner Hauptstraße 48, 5020 Salzburg, Austria; Procomcure Biotech GmbH, Austria.
authors.forename: Kamil
authors.initials: K
authors.lastname: Önder
authors.affiliation: 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.
authors.forename: Barbara
authors.initials: B
authors.lastname: Kofler
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D007211:Indoles / Q000633:toxicity*; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D051379:Mice; D017628:Microglia / Q000187:drug effects; D009474:Neurons / Q000187:drug effects; D044093:Receptor, Galanin, Type 3 / Q000037:antagonists & inhibitors*
chemical_list: C510288:1-phenyl-3-((3-(trifluoromethyl)phenyl)imino)-1H-indol-2-one; D007211:Indoles; D044093:Receptor, Galanin, Type 3
keywords: Anxiety; Cytotoxicity; Depression; Galanin; Galanin receptor 3; SNAP 37889