二氢埃托啡耐受后小鼠脑内cAMP含量的减少及氨基酸含量的增加  

Decrease of cAMP and increase of amino acids contents in mouse brain after dihydroetorphine tolerance

作　　者：陈明辉[1] 李其松[1] 沈煜 马鸿建 左晓洁 

机构地区：[1]上海医科大学基础医学院医学神经生物学国家重点实验室

出　　处：《中国药理学报》1998年第1期91-93,共3页Acta Pharmacologica Sinica

摘　　要：目的：探讨二氢埃托啡（ＤＨＥ）耐受的机制．方法：放免法及反相高效液相色谱荧光检测法测定环腺苷一磷酸（ｃＡＭＰ）及谷氨酸（Ｇｌｕ）、门冬氨酸（Ａｓｐ）、谷氨酰氨（Ｇｌｎ）、ＧＡＢＡ的含量．结果：ＤＨＥ反复ｓｃ８ｄ后产生耐受．小鼠去小脑全脑Ｇｌｕ、Ａｓｐ、ＧＡＢＡ的基础含量分别由对照组的１４１±２１、３０±０４、１８±０８升高至耐受组的１７２±２２、４１±０６、３２±１０μｍｏｌ／ｇ组织，Ｇｌｎ的含量无明显改变．下丘脑及纹状体的ｃＡＭＰ基础含量分别由对照组的２７１±３８、１８９±３１降至耐受组的９６±１５、６５±２１ｎｍｏｌ／ｇ组织，大脑皮层ｃＡＭＰ的含量无明显改变．结论：ＤＨＥ耐受与脑内Ｇｌｕ、Ａｓｐ、ＧＡＢＡ基础含量的升高及下丘脑、纹状体内ｃＡＭＰ的基础含量的降低有关．AIM: To study the mechanism of dihydroetorphine (DHE) tolerance. METHODS: DHE tolerance was produced by repeated sc injections in progressively increased doses to mice for 8 d. The concentrations of amino acids and cAMP were detected by RP HPLC/fluorescence assay and radioimmunoassay, respec￣tive￣ly. RESULTS: The basal contents of glutamic acid (Glu), aspartic acid (Asp), and GABA in whole brain (cerebellum removed) were increased respectively from 14 1±2 1, 3 0±0 4, and 1 8±0 8 μmol/g tissue in control mice to 17 2±2 2, 4 1±0 6, and 3 2±1 0 μmol/g tissue in tolerant mice, and the rates of increase were 22 0 % ( P <0 05), 36 7 % ( P <0 01), and 77 8 % ( P <0 05 vs control), respectively. There was no significant difference in the basal contents of Gl n (5 1±1 0 vs 4 5±1 7 μmol/g tissue of control). The basal contents of cAMP in hypothalamus and striatum were decreased respectively from 271±38 and 189±31 nmol/g tissue in control mice to 96±15 and 65±21 nmol/g tissue in tolerant mice ( P <0 01), and the rates of decrease were 64 6 % and 65 6 %, respectively. There was no significant difference of cAMP in cerebral cortex (72±20 vs 55±15 nmol/g tissue of control). CONCLUSION: The increases of Glu, Asp, and GABA in brain and the decrease of cAMP in hypothalamus and striatum were involved in DHE tolerance.

关 键 词：二氢埃托啡 药物耐受性 CAMP 氨基酸 

分 类 号：R971.2[医药卫生—药品]