可乐定预处理引起豚鼠回肠对WIN 55,212-2脱敏

F. Rezania, L. Mohaghegh Shalmani, R. Rahimian, A. R. Dehpour, S. Ejtemaei Mehr
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引用次数: 0

摘要

考虑到除了吗啡与WIN 55,212-2有相同的相互作用外,还存在可乐定与吗啡的交叉耐受,我们在豚鼠回肠中验证了WIN 55,212-2与可乐定之间存在交叉耐受这一事实,这是检验大麻素和α2-腺受体激动剂作用方式的著名模型。将矩形脉冲传递到0.5 g拉伸的回肠节段,并固定在20 ml器官液中。使用PowerLab系统和Graphpad Prism记录抽搐并分析数据。WIN 55,212-2和可乐定对电诱发收缩的抑制呈剂量依赖性(pD2分别为8.56±0.41和7.65±0.15)。win55,212 -2 (3 × IC50)孵育4 h可诱导对该效应的耐受(pD2 = 6.36±0.26,耐受度:159.32)(P <0.01),而可乐定(2 × IC50和4 × IC50)在不同时间疗程中无显著差异。与未处理的组织相比,与可乐定(3 × 10−10m)孵育4 h后,WIN 55,212-2的抑制作用剂量-反应曲线向右移动(pD2 = 5.26±0.69,耐受度:2000)(P <0.001)。这一观察结果为大麻素-去甲肾上腺素能系统在肠神经系统中的相互作用作为中枢神经系统的简化代表提供了证据。
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Pretreatment with clonidine caused desensitization to WIN 55,212-2 in guinea pig ileum

  1. Considering the existence of cross-tolerance between clonidine and morphine besides the same interaction between morphine and WIN 55,212-2 persuaded us to verify this fact between WIN 55,212-2 and clonidine in guinea pig ileum, which is a well-known model to examine the mode of action of cannabinoids and α2-adenoceptor agonists
  2. The rectangular pulses were passed to the 0.5 g stretched ileum segments that were fixed in 20-ml organ bath. PowerLab system and Graphpad Prism were applied to record twitches and analyse the data. Electrically evoked contractions were dose-dependently inhibited by WIN 55,212-2 and clonidine (pD2= 8.56 ± 0.41 and 7.65 ± 0.15, respectively).
  3. Tolerance to this effect could be induced by 4-h incubation with WIN 55,212-2 (3 × IC50) (pD2 = 6.36 ± 0.26, degree of tolerance: 159.32) (< 0.01) but not with clonidine (2 × IC50 and 4 × IC50) for different time courses. Dose–response curve for inhibitory action of WIN 55,212-2 was shifted to the right after 4-h incubation with clonidine (3 × 10−10m) comparing to the untreated tissues (pD2 = 5.26 ± 0.69, degree of tolerance: 2000) (< 0.001). This observation provides the evidence for the cannabinoid-noradrenergic systems interaction in the enteric nervous system as a simplified representative for central nervous system.
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Issue Information Autonomic and Autacoid Pharmacology: Goodbye and thank you Attenuation of the anti-contractile effect of cooling in the rat aorta by perivascular adipose tissue Retraction: Dopamine receptor immunohistochemistry in the rat choroid plexus. Issue Information
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