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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 observe the effect of agmatine on desensitization and down-regulation of μ-opioid receptor induced by opioid preconditioning by activating I1 imidazoline receptor. Methods: CHO-μ and CHO-μ / IRAS (imidazoline receptor antisera-selected protein) cells were used as research objects, and treated with [35S] GTPγS and diprenorphine Combined with experimental methods, the effect of agmatine-I1 imidazoline receptor system on desensitization and down-regulation of μ-opioid receptor was determined. Results: There was no significant difference in the amount of μ-opioid receptor expression and affinity for the ligand between normal CHO-μ and CHO-μ / IRAS cells; the response of μ-opioid receptors to agonist stimulation was consistent in both cells. CHO-μ / IRAS cells were exposed to opiate receptor agonist DAMGO (D-Ala2, N-Me-Phe4, Gly5-ol) and enkephalin at 10μmol / , While agmatine (10 nmol / L ~ 100 μmol / L) did not affect the desensitization of μ-opioid receptor. DAMGO (1μmol / L) treatment of two cells 12h after the emergence of μ-opioid receptor down, agmatine (1 ~ 100nmol / L) concentration-dependent inhibition of μ-opioid receptor CHO- μ / IRAS cells , While the same concentration of agmatine had no effect in CHO-μ cells. Agmatine is blocked by the I1 imidazoline receptor blocker efaroxan (Efa). CONCLUSION: Agmatine inhibits the down-regulation of μ-opioid receptor induced by long-term treatment of DAMGO through activation of I1 imidazoline receptor, which may be related to the inhibition of opiate dependence by agmatine.