Lessons on the sigma-1 receptor in tnbs-induced rat colitis: Modulation of the uchl-1, il-6 pathway

Nikoletta Almási, Szilvia Török, Szabolcs Dvorácskó, Csaba Tömböly, Ákos Csonka, Zoltán Baráth, Zsolt Murlasits, Zsuzsanna Valkusz, Anikó Pósa, Csaba Varga, Krisztina Kupai

Research output: Contribution to journalArticle

Abstract

Inflammatory Bowel Disease (IBD) is an autoimmune ailment of the gastrointestinal (GI) tract, which is characterized by enhanced activation of proinflammatory cytokines. It is suggested that the sigma-1 receptor (σ1R) confers anti-inflammatory effects. As the exact pathogenesis of IBD is still unknown and treatment options are limited, we aimed to investigate the effects of σ1R in 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced experimental colitis. To this end, male Wistar– Harlan rats were used to model colitic inflammation through the administration of TNBS. To investigate the effects of σ1R, Fluvoxamine (FLV, σ1R agonist) and BD1063 (σ1R antagonist) were applied via intracolonic administration to the animals once a day for three days. Our radioligand binding studies indicated the existence of σ1Rs as [3H](+)-pentazocine binding sites, and FLV treatment increased the reduced σ1R maximum binding capacity in TNBS-induced colitis. Furthermore, FLV significantly attenuated the colonic damage, the effect of which was abolished by the administration of BD1063. Additionally, FLV potentially increased the expression of ubiquitin C-terminal hydrolase ligase-1 (UCHL-1) and the levels of endothelial nitric oxide synthase (eNOS), and decreased the levels of interleukin-6 (IL-6) and inducible NOS (iNOS) expression. In summary, our study offers evidence for the anti-inflammatory potential of FLV and σ1R in experimental colitis, and our results present a promising approach to the development of new σ1R-targeted treatment options against IBD.

Original languageEnglish
Article number4046
Pages (from-to)1-21
Number of pages21
JournalInternational journal of molecular sciences
Volume21
Issue number11
DOIs
Publication statusPublished - Jun 1 2020

Keywords

  • Fluvoxamine
  • Inflammation
  • Sigma receptor
  • UCHL-1

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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