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.
