Andrews P L, Davis C J, Bingham S, Davidson H I, Hawthorn J, Maskell L
Department of Physiology, St. George's Hospital Medical School, London, UK.
Can J Physiol Pharmacol. 1990 Feb;68(2):325-45. doi: 10.1139/y90-047.
In recent years the role of the area postrema in the emetic reflex has been predominant and the involvement of the abdominal visceral innervation has tended to be overlooked. This paper attempts to redress the balance reflex by reviewing aspects of the existing literature and complementing this with original studies from the ferret. In view of the widespread use of the ferret in studies of emesis and particularly in the characterization of the antiemetic actions of 5-HT3 receptor antagonist, the opportunity is taken to assess the suitability of this species for studies of emesis. It is concluded that the ferret is sensitive to a wide range of emetic stimuli including intragastric irritants, opiate and dopamine receptor agonists, many cytotoxic drugs, and radiation. For several stimuli it is more sensitive than other species and for radiation on the basis of its ED100 it appears to be the most sensitive of the laboratory animals studied. Using electrical stimulation of the central end of the dorsal vagal trunk in the abdomen in conscious and anaesthetized animals, the vagal afferents were shown to be capable of eliciting emesis. Using lesioning studies an involvement of the vagus in the emetic response to a number of cytotoxic drugs (e.g., cisplatinum, cyclophosphamide, mustine) and radiation was demonstrated, although the magnitude of the effect varied with the different stimuli. An attempt is made to reconcile these observations with previous studies of area postrema ablation. The problems of interpreting the effects of nerve lesions are critically discussed in light of preliminary evidence presented here that there may be a degree of plasticity in the emetic pathway following such lesions. The range of antiemetic effects of 5-HT3 receptor antagonists is reviewed and an attempt is made to identify the site(s) at which these agents act. Results are presented that suggest a link between the vagus and 5-HT3 receptor antagonism. These studies are discussed together with others and lead us to propose that (in the ferret) 5-HT3 receptor antagonists have their main antiemetic effect by acting on vagal afferent terminals in the wall of the upper gut with an additional minor site either in the nucleus tractus solitarius or presynaptically on the vagal afferent terminals in the medulla where binding sites for 5-HT3 receptor ligands have recently been demonstrated in this species.
近年来，最后区在催吐反射中的作用占主导地位，而腹部内脏神经支配的参与往往被忽视。本文试图通过回顾现有文献的各个方面并辅以雪貂的原始研究来纠正这种平衡。鉴于雪貂在呕吐研究中被广泛使用，尤其是在5-HT3受体拮抗剂止吐作用的表征方面，本文借此机会评估该物种在呕吐研究中的适用性。结论是，雪貂对多种催吐刺激敏感，包括胃内刺激物、阿片类和多巴胺受体激动剂、许多细胞毒性药物以及辐射。对于几种刺激，它比其他物种更敏感，就其ED100而言，对于辐射它似乎是所研究的实验动物中最敏感的。通过对清醒和麻醉动物腹部迷走神经干中枢端进行电刺激，发现迷走神经传入纤维能够引发呕吐。通过损伤研究表明，迷走神经参与了对多种细胞毒性药物（如顺铂、环磷酰胺、氮芥）和辐射的呕吐反应，尽管效应的程度因不同刺激而异。本文试图将这些观察结果与先前关于最后区切除的研究相协调。鉴于此处提出的初步证据表明，神经损伤后催吐途径可能存在一定程度的可塑性，因此对解释神经损伤效应的问题进行了批判性讨论。本文回顾了5-HT3受体拮抗剂的止吐作用范围，并试图确定这些药物的作用位点。结果表明迷走神经与5-HT3受体拮抗作用之间存在联系。本文将这些研究与其他研究一起进行讨论，并使我们提出（在雪貂中）5-HT3受体拮抗剂的主要止吐作用是通过作用于上消化道壁的迷走神经传入终末，在孤束核或延髓中迷走神经传入终末的突触前有一个额外的次要位点，最近在该物种中已证明存在5-HT3受体配体的结合位点。
