Effect of sumatriptan on acetic acid-induced experimental colitis in rats: a possible role for the 5‐HT1B/1D receptors

Abstract

Mucosal inflammation in colitis is associated with changes in the intestinal serotonin (5-HT) level. Sumatriptan, a 5-HT1B/1D receptor agonist, has demonstrated anti-inflammatory characteristics. The purpose of this study was to determine the effects of sumatriptan in a rat model of acute experimental colitis and to elucidate theprobable participation of presynaptic 5-HT1B/1D receptors. To induce colitis, acetic acid (4%) was injected intrarectally. Treatments were given intraperitoneally (IP) once daily over 3 consecutive daysstarting 1-h post-induction. Sumatriptan was given at 0.5, 1, 2, and 5mg/kg. GR-127935, a 5-HT1B/1D receptor antagonist, was injected (0.1 and 0.3mg/kg) 30min prior to the most effective dose of sumatriptan (1mg/kg). On day 4, the colon samples were isolated. Significant enhancements of the tissue tumor necrosis factor-alpha (TNF-α), myeloperoxidase (MPO), microscopicand macroscopic damages, body weight losses, and also reductions in tissue superoxide dismutase (SOD) and 5-HT were observed in colitis rats. On the other hand, sumatriptan at doses 0.5, 1, and 2mg/kg could diminish pathologic changes in the measured biomarkers, histopathologic damages, and body weight losses. Although GR-127935 at dose 0.3mg/kg could markedly improve the pathologic indexes, its sub-effective dose (0.1mg/kg) reversed the protective effect of sumatriptan (1mg/kg). Moreover, sumatriptan (1 and 5mg/kg) and GR-127935 (0.3mg/kg) increased the serotonin level. Post-treatment with low-dose sumatriptan demonstrated a protective impact on this peripheral inflammatory condition. Notably, this protective effect may be mediated, at least in part, through 5-HT1B/1D receptors, as well as anti-inflammatory and anti-oxidative characteristics.