NO对去甲吗啡在离体豚鼠回肠上依赖性耐受性产生的作用  

Effect of nitric oxide (NO) on dependence and tolerance of normorphine (NM) in the guinea-pig ileum in vitro

作　　者：周明正[1] 李艳娜[1] 

机构地区：[1]同济大学基础医学院生理学教研室,上海200331

出　　处：《中国药理学通报》2001年第2期194-196,共3页Chinese Pharmacological Bulletin

摘　　要：目的观察 ＮＯ合酶（ ＮＯ ｓｙｎｔｈａｓｅ，ＮＯＳ）抑制剂左旋硝基精氨酸（ＮＧ－ｎｉｔｒｏ－Ｌ－ａｒｇｉｎｉｎｅ，ＮＯＡｒｇ）和 ＮＯ合成前体左旋精氨酸（Ｌ－ａｒｇｉｎｉｎｅ，Ｌ－Ａｒｇ）对去甲吗啡（ｎｏｒｍｏｒｐｈｉｎｅ，ＮＭ）在离体豚鼠回肠上依赖性耐受性产生的影响，研究ＮＯ在阿片类药物依赖性耐受性产生中的作用。方法以离休豚鼠回肠为实验对象，４℃孵育６ ｈ， ２４ ｈ后，分别测定纳洛酮（ｎａｌｏｘｏｎｅ，Ｎｘ）与氯化乙酰胆碱（ａｃｅｔｙｌｃｈｏｌｉｎｅ，Ａｃｈ）引起的收缩高度比值，作为依赖性产生的指标。在耐受性产生实验中，分别测定回肠空白组和药物组４℃孵育３ｈ后对ＮＭ抑制电刺激收缩的剂量反应曲线。结果回肠分别经ＮＭ，ＮＭ加ＮＯＡｒｇ，ＮＭ加Ｌ－Ａｒｇ中孵育６ｈ后，纳洛酮均可使其产生戒断收缩，且两组与Ａｃｈ的收缩高度比值差异无显著性（ｎ＝６）， Ｐ＞０．０５。而孵育２４ ｈ后，ＮＭ，ＮＭ加 Ｌ－Ａｒｇ组收缩高度比值分别为 ０． ８９±０． ０２， ０． ９０±０． ０２， Ｐ＞ ０． ０５，而ＮＭ加ＮＯＡｒｇ药物组对纳洛酮的戒断收缩反应明显减弱，收缩高度比值为 ０．４７± ０．０５（ｎ＝ ６， Ｐ＜ ０．０１）。可见ＮＭ加ＮＯＡ?AIM To study the effect of NO on dependence and tolerance of NM in the guinea pig ileum in vitro. METHODS The segment of the guinea pig ileum were suspended in organ chambers for measuring withdrawal responses are expressed as ratio of naloxone(100 nmol· L-1)and Ach (100 nmol · L-1) contraction responses and measuring inhibitory effects of NM for contractions evoked by electric stimulation. RESULTS After the segment of the ileum was incubated With NM (200 nmol· L- 1 ), NM (200 nmol· L-1) plus L-Arg (0.1 mmol· L-1), at 4℃ for 24 h respectively, the ratio are 0.89 ± 0.02, 0.90± 0.02, (n = 6) P >0.05. The ratio of NM (200 nmol· L-l) plus NOArg (0.1 mmol. L-1 ) is 0.47 ± 0.05, compared with control (n = 6, P < 0 .01 ). After the segment of the ileum was incubated with NM (500 nmol· L-1 ), NM (500 nmol· L-1 ) plus L-Arg (0. 1 mmol·L-1) at 37℃ for 3 h respectively, the sensitivities of the preparations for NM were reduced significantly, their concentration- response curves were shift to right (P < 0 .01 ). In the segment of the ileum incubaled with NM (500 nmol· L-１) and NG-nitro－L-Arginime (NOArg 0. 1 mmol . L- 1 ) at 37℃ for 3 h, the sensitivities of the preparations for NM was unchange (P >0 .05). CONCLUSIONS These results suggest that NO has important role on dependence and tolerance of NM in the guinea Pig ileum.

关 键 词：离体豚鼠 回肠 去甲吗啡 药物依赖性 药物耐受性 

分 类 号：R971.2[医药卫生—药品]