Kan Kelvin K W, Wai Man K, Jones Robert L, Rudd John A
Department of Pharmacology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR, China.
Cardiovascular Research Group, Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow G1 0NR, UK.
Eur J Pharmacol. 2017 May 15;803:112-117. doi: 10.1016/j.ejphar.2017.03.035. Epub 2017 Mar 16.
Prostanoid EP receptor agonists are used for a number of clinical indications but may be associated with gastric disturbance. In the present studies we used the ferret and sulprostone (30µg/kg, i.p.) to investigate the role of EP receptors in mechanisms of emesis and defaecation. The emetic response was antagonized significantly by (+)-(2S,3S)-3-(2-methoxybenzylamino)-2-phenlypiperidine hydrochloride (CP-99,994; 10mg/kg, i.p.; P<0.05), but not by metoclopramide (0.3 and 3mg/kg), ondansetron (0.1 and 1mg/kg), or scopolamine (3mg/kg); promethazine (3mg/kg) potentiated emesis by approximately 82% (P<0.05). Out of the drugs tested, only scopolamine (3mg/kg) reduced significantly the defaecatory and/or tenesmus response (P<0.05). Bilateral abdominal vagotomy was ineffective to reduce sulprostone (30µg/kg, i.p.)-induced emesis and defaection and/or tenesmus. However, sulprostone (10µg, i.c.v.) administered into the fourth ventricle was emetic but did not induce defaection or tenesmus. These data suggests that the action of sulprostone to induce emesis and defaecation and/or tenesmus is largely independent of the abdominal vagal system, with emesis involving central mechanisms. Emetic mechanisms appear dissociated from those mediating defaecation and/or tenesmus.
前列腺素EP受体激动剂可用于多种临床适应症，但可能与胃部不适有关。在本研究中，我们使用雪貂和硫前列酮（30μg/kg，腹腔注射）来研究EP受体在呕吐和排便机制中的作用。（+）-（2S，3S）-3-（2-甲氧基苄基氨基）-2-苯基哌啶盐酸盐（CP-99,994；10mg/kg，腹腔注射；P<0.05）可显著拮抗呕吐反应，但甲氧氯普胺（0.3和3mg/kg）、昂丹司琼（0.1和1mg/kg）或东莨菪碱（3mg/kg）则不能；异丙嗪（3mg/kg）使呕吐增强约82%（P<0.05）。在所测试的药物中，只有东莨菪碱（3mg/kg）能显著降低排便和/或里急后重反应（P<0.05）。双侧腹部迷走神经切断术对减轻硫前列酮（30μg/kg，腹腔注射）诱导的呕吐和排便及/或里急后重无效。然而，向第四脑室内注射硫前列酮（10μg）可引起呕吐，但不诱发排便或里急后重。这些数据表明，硫前列酮诱导呕吐和排便及/或里急后重的作用在很大程度上独立于腹部迷走神经系统，呕吐涉及中枢机制。呕吐机制似乎与介导排便和/或里急后重的机制不同。
