Further investigation of the effects of 5-hydroxytryptamine, 8-OH-DPAT and DOI to mediate contraction and relaxation responses in the intestine and emesis in Suncus murinus

Abstract

5-HT receptors are implicated in many gastrointestinal disorders. However, the precise role of 5-HT in mediating GI responses in Suncus murnius is still unclear. Therefore in this study, the effects of 5-HT and its agonists were investigated in Suncus. The involvement of 5-HT_2C receptors in mediating emesis was also investigated. The ability of 5-HT and its agonists/antagonists at 5-HT_1A and 5-HT₂ to modify GI motility was investigated in vitro and in vivo. WAY100635 (a 5-HT_1A antagonist) inhibited the contraction response to 5-HT in the proximal segments without affecting the maximum response; whilst enhancing the contraction to 5-HT (>30.0nM) in the distal intestine. The selective 5-HT_2A and 5-HT_2B receptor antagonists MDL-100907 and RS-127445 attenuated 5-HT-induced contractions (<10.0µM) in the distal segments. RS-127445 also attenuated 5-HT-induced contractions in the central segments. The selective 5-HT_2C receptor antagonist SB-242084, attenuated the responses to 5-HT (> 3.0nM) in the proximal and central but not the distal regions. 8-OH-DPAT-induced relaxation was resistant to the antagonism by 5-HT_1A/7 antagonists. DOI in the presence of 5-HT_1A/2A/2B/2C antagonists induced greater contraction responses (>1.0µM) in most tissues, whilst RS-127445, or SB-242084, reduced the responses to DOI (< 1.0µM) in some tissues. SB-242084 also suppressed emesis-induced by motion and intragastric CuSO₄. In conclusion, within different regions of intestine, 5-HT₂ receptors are differently involved in contraction and emetic responses and that 8-OH-DPAT induces relaxation via non-5-HT_1A/7 receptors. Suncus could provide a model to investigate these diverse actions of 5-HT.

Keywords: 5-HT(1A) and 5-HT(2) receptor subtypes; 5-Hydroxytryptamine; 8-OH-DPAT; DOI; Suncus murinus intestine.