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

Farideh A. Javid; Saeed Afshin-javid; Charles C. Horn

doi:10.1016/j.ejphar.2017.12.051

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

Farideh A. Javid, Saeed Afshin-javid, Charles C. Horn

Research output: Contribution to journal › Article

1 Citation (Scopus)

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
Pages (from-to)	79-87
Number of pages	9
Journal	European Journal of Pharmacology
Volume	821
Early online date	23 Dec 2017
DOIs	https://doi.org/10.1016/j.ejphar.2017.12.051
Publication status	Published - 15 Feb 2018

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8-Hydroxy-2-(di-n-propylamino)tetralin

Intestines

Vomiting

Serotonin 5-HT1 Receptor Antagonists

Serotonin

Serotonin Receptor Agonists

Receptor, Serotonin, 5-HT2B

Receptor, Serotonin, 5-HT2C

Emetics

Serotonin 5-HT2 Receptor Antagonists

Serotonin Receptors

hydroxide ion

Cite this

Javid, F. A., Afshin-javid, S., & Horn, C. C. (2018). 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. European Journal of Pharmacology, 821, 79-87. https://doi.org/10.1016/j.ejphar.2017.12.051

Javid, Farideh A. ; Afshin-javid, Saeed ; Horn, Charles C. / 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. In: European Journal of Pharmacology. 2018 ; Vol. 821. pp. 79-87.

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title = "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-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.",

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Javid, FA, Afshin-javid, S & Horn, CC 2018, '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', European Journal of Pharmacology, vol. 821, pp. 79-87. https://doi.org/10.1016/j.ejphar.2017.12.051

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. / Javid, Farideh A.; Afshin-javid, Saeed; Horn, Charles C.

In: European Journal of Pharmacology, Vol. 821, 15.02.2018, p. 79-87.

Research output: Contribution to journal › Article

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AU - Horn, Charles C.

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AB - 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.

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