胍丁胺-I1咪唑啉受体对μ-阿片受体脱敏和下调的影响  

Modulating effect of agmatine on desensitization and down-regulation of μ-opioid receptor by activation of I1 imidazoline receptor

作　　者：高燕[1] 吴宁[1] 李斐[1] 王勃[1] 徐波[1] 苏瑞斌[1] 李锦[1] 

机构地区：[1]军事医学科学院毒物药物研究所,北京100850

出　　处：《军事医学科学院院刊》2007年第5期411-415,共5页Bulletin of the Academy of Military Medical Sciences

基　　金：国家重点基础研究发展计划("973"计划)资助项目(2003CB515400)

摘　　要：目的:观察胍丁胺通过激活I1咪唑啉受体对阿片预处理引起的μ-阿片受体脱敏和下调的影响。方法:以CHO-μ和CHO-μ/IRAS(imidazoline receptor antisera-selected protein,咪唑啉受体抗血清选择性蛋白)细胞作为研究对象,用[35S]GTPγS和3H-二丙诺啡(diprenorphine)结合实验方法,确定胍丁胺-I1咪唑啉受体作用系统对μ-阿片受体脱敏和下调的影响。结果:在正常CHO-μ和CHO-μ/IRAS细胞中,μ-阿片受体的表达量和对配体的亲和力无显著差异;两细胞中μ-阿片受体对激动剂刺激的反应一致。阿片受体激动剂DAMGO[(D-Ala2,N-Me-Phe4,Gly5-ol)-脑啡肽(enkephalin),10μmol/L]处理CHO-μ/IRAS细胞30 minμ-阿片受体出现脱敏,而胍丁胺(10 nmol/L^100μmol/L)不影响μ-阿片受体脱敏过程。DAMGO(1μmol/L)处理两细胞12 h后可出现μ-阿片受体的下调,胍丁胺(1~100 nmol/L)浓度依赖性地抑制CHO-μ/IRAS细胞中μ-阿片受体的下调,而相同浓度胍丁胺在CHO-μ细胞中无此作用。胍丁胺这一作用能被I1咪唑啉受体阻断剂依法克生(efaroxan,Efa)所阻断。结论:胍丁胺通过激活I1咪唑啉受体可抑制DAMGO长期处理所致的μ-阿片受体下调,此作用可能与胍丁胺抑制阿片依赖有关。Objective： To investigate the effects of agmatine by activation of I1 imidazoline receptor on DAMGO [ （ DAla^2 ,N-Me-Phe^4 ,Gly^5-ol）-enkephalin ]-induced desensitization and down-regulation of μ-opioid receptor. Methods： Two cell lines, Chinese hamster ovary cells expressing μ-opioid receptor alone （ CHO-μ） and co-expressing μ-opioid receptor and imidazoline receptor antisera-selected protein （IRAS）, CHO-μ/IRAS i. e. a candidate for I1 imidazoline receptor, were used. [ 35↑S ] GTPγS binding assay and [ 3↑H ] diprenorphine binding assay were used to determine the effect on the desensitization and down-regulation of μ-opioid receptor by the agrnatine-I1 imidazoline receptor system. Results： There was no significant difference in expression and affinity of μ-opioid receptor between normal CHO-μ and CHO-Iμ /IRAS cells. The reaction of μ-opioid receptor in both cells was equal to the stimulation of ligand. DAMGO 10 μmol/L treatment for 30 min induced desensitization of μ-opioid receptor in CHO-μ/IRAS cells, while agmatine（ 10 nmol/L - 10 μmol/L） did not influence DAMGO-induced desensitization of μ-opioid receptor. Chronic treatment with DAMGO （ 1 μmol/L, 12 h） decreased the expression of μ-opioid receptor in CHO-μ and CHO-μ/IRAS cells. Agmatine （1 -100 nM） concentration-dependently inhibited DAMGO-induced down-regulation of μ-opioid receptor in CHO-μ/IRAS cells, while this effect was not observed in CHO-μcells. Efaroxan, an I1 imidazoline receptor-preferential antagonist, completely reversed the effect of ag- matine in CHO-μ/IRAS cell. Conclusion： Agmatine could inhibit DAMGO-induced down-regulation of μ-opioid receptor by activation of I1 imidazoline receptor, which may contribute to the inhibition of opioid dependence by agmatine.

关 键 词：胍丁胺 I1咪唑啉受体 Μ-阿片受体 脱敏 下调 

分 类 号：R96[医药卫生—药理学]