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.
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.
复制标题
进一步研究 5-羟色胺、8-OH-DPAT 和 DOI 对介导 Suncus murinus 肠道收缩和松弛反应以及呕吐的影响。
DOI：
10.1016/j.ejphar.2017.12.051
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发表时间：
2018
影响因子：
5
通讯作者：
Horn,CharlesC
中科院分区：
文献类型：
--
作者：
Javid,FaridehA;Afshin-Javid,Saeed;Horn,CharlesC
5-HT 受体与许多胃肠道疾病有关。然而，5-HT 在介导 Suncusmurniusis 胃肠道反应中的确切作用仍不清楚。因此，在本研究中，研究了 5-HT 及其激动剂在 Suncus 中的作用。还研究了 5-HT2C 受体在介导呕吐中的作用。在体外和体内研究了 5-HT 及其 5-HT1A 和 5-HT2 激动剂/拮抗剂改变胃肠道运动的能力。WAY100635（5-HT1A 拮抗剂）抑制近端节段对 5-HT 的收缩反应，而不影响最大反应；同时增强远端肠道中 5-HT (>30.0 nM) 的收缩。选择性 5-HT2A 和 5-HT2B 受体拮抗剂 MDL-100907 和 RS-127445 可减弱远端节段中 5-HT 诱导的收缩 (<10.0 µM)。 RS-127445 还减弱了 5-HT 诱导的中央节段收缩。选择性 5-HT2C 受体拮抗剂 SB-242084 可减弱近端和中央区域对 5-HT (> 3.0 nM) 的反应，但不会减弱远端区域。 8-OH-DPAT 诱导的松弛对 5-HT1A/7 拮抗剂的拮抗作用具有抵抗力。在 5-HT1A/2A/2B/2Cantagonists 存在下，DOI 在大多数组织中诱导更大的收缩反应 (>1.0 µM)，而 RS-127445 或 SB-242084 则降低了某些组织对 DOI 的反应 (<1.0 µM)。 SB-242084 还抑制运动和胃内 CuSO4 引起的呕吐。总之，在肠道的不同区域内，5-HT2 受体不同地参与收缩和催吐反应，并且 8-OH-DPAT 诱导松弛 vianon-5-HT1A/7 受体。Suncus 可以提供一个模型来研究 5-HT 的这些不同作用。
5-HT receptors are implicated in many gastrointestinal disorders. However, the precise role of 5-HT in mediating GI responses inSuncusmurniusis still unclear. Therefore in this study, the effects of 5-HT and its agonists were investigated inSuncus. The involvement of 5-HT2Creceptors in mediating emesis was also investigated. The ability of 5-HT and its agonists/antagonists at 5-HT1Aand 5-HT2to modify GI motility was investigatedin vitroandin vivo.WAY100635 (a 5-HT1Aantagonist) 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-HT2Aand 5-HT2Breceptor 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-HT2Creceptor 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/7antagonists. DOI in the presence of 5-HT1A/2A/2B/2Cantagonists 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-HT2receptors are differently involved in contraction and emetic responses and that 8-OH-DPAT induces relaxationvianon-5-HT1A/7receptors.Suncuscould provide a model to investigate these diverse actions of 5-HT.