In vitro toxicity of the galanin receptor 3 antagonist SNAP 37889. (April 2016)

• Record Type: Journal Article
• Authors: Koller, Andreas; Rid, Raphaela; Beyreis, Marlena; Bianchini, Rodolfo; Holub, Barbara S.; Lang, Andreas; Locker, Felix; Brodowicz, Bernhard; Velickovic, Ognjen; Jakab, Martin; Kerschbaum, Hubert; Önder, Kamil; Kofler, Barbara
• Is Part Of: Neuropeptides. Volume 56(2016)
• Page Start: 83
• Page End: 88
• Publication Date: 2016-04
• Subjects: Galanin -- Galanin receptor 3 -- SNAP 37889 -- Cytotoxicity -- Anxiety -- Depression; Neuropeptides -- Periodicals; Neuropeptides; Neuropeptides -- Périodiques; Neuropeptides; Electronic journals; Periodicals; 572.65
• DOI: 10.1016/j.npep.2015.12.003
• Languages: English
• ISSNs: 0143-4179

Abstract

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 (≥ 10 μM) 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. Highlights: SNAP 37889 produces toxic effects in vitro . The toxicity of SNAP 37889 does not depend on endogenous expression of galanin receptors. Immune cells are sensitive to SNAP 37889-induced cell death.