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-HT2C receptors in mediating emesis was also investigated. The ability of 5-HT and its agonists/antagonists at 5-HT1A and 5-HT2 to modify GI motility was investigated in vitro and in vivo.
WAY100635 (a 5-HT1A antagonist) inhibited the contraction response to 5-HT in the proximal segments without affecting the maximum response; whilst enhancing the contraction to 5-HT (>30.0 nM) in the distal intestine. The selective 5-HT2A and 5-HT2B receptor antagonists MDL-100907 and RS-127445 attenuated 5-HT-induced contractions (<10.0 µM) in the distal segments. RS-127445 also attenuated 5-HT-induced contractions in the central segments. The selective 5-HT2C receptor antagonist SB-242084, attenuated the responses to 5-HT (> 3.0 nM) in the proximal and central but not the distal regions. 8-OH-DPAT-induced relaxation was resistant to the antagonism by 5-HT1A/7 antagonists. DOI in the presence of 5-HT1A/2A/2B/2C antagonists induced greater contraction responses (>1.0 µM) in most tissues, whilst RS-127445, or SB-242084, reduced the responses to DOI (< 1.0 µM) 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-HT1A/7 receptors. Suncus could provide a model to investigate these diverse actions of 5-HT.
Original language | English |
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Pages (from-to) | 79-87 |
Number of pages | 9 |
Journal | European Journal of Pharmacology |
Volume | 821 |
Early online date | 23 Dec 2017 |
DOIs | |
Publication status | Published - 15 Feb 2018 |
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Farideh Javid
- Department of Pharmacy - Reader
- School of Applied Sciences
- Pharmacology and Therapeutics Centre - Member
- Institute of Skin Integrity and Infection Prevention - Associate Membership
Person: Academic