Long-term blockade of brain opioid receptors by the opiate antagonist naltrexone increases methionine-enkephalin content in the striatum and nucleus accumbens (Tempel et al., 1984). To determine whether these changes in peptide levels reflect increased peptide synthesis, we examined preproenkephalin mRNA content in discrete brain regions of control (placebo-treated) and chronic naltrexone-treated animals by Northern analysis. Chronic naltrexone treatment (8 d) led to an approximately 12-fold increase in the striatal content of preproenkephalin mRNA relative to that of control animals. In contrast, no statistically significant change was observed in striatal mRNA for cyclophilin (1B15) or actin. Small increases in preproenkephalin mRNA content occurred in the hippocampus (+40%) and hypothalamus (+19%). No significant changes occurred in the frontal cortex. Increases in levels of the mRNA were seen as early as 24 hr after antagonist treatment. In contrast, changes in opioid receptor density required 3-4 d to reach half-maximal up-regulation after chronic antagonist treatment. Recent evidence has suggested that substance P is regulated by opioid peptides. To determine whether substance P synthesis is altered by chronic antagonist treatment, the mRNA corresponding to the precursor for substance P was examined using a probe for exon-7 of the preprotachykinin gene. Preprotachykinin mRNA content in the striatum was increased 6-fold after chronic antagonist treatment relative to that of control animals. Substance P content was increased 3-fold after chronic antagonist treatment. These data suggest that chronic blockade of brain opioid receptors leads to the increased synthesis of both enkephalin and substance P in the striatum and that these changes are relatively specific.(ABSTRACT TRUNCATED AT 250 WORDS)

译文

鸦片拮抗剂纳曲酮对脑阿片受体的长期阻断增加纹状体和伏隔核中的蛋氨酸-脑啡肽含量 (Tempel等,1984)。为了确定肽水平的这些变化是否反映了肽合成的增加,我们通过Northern分析检查了对照组 (安慰剂治疗) 和慢性纳曲酮治疗动物的离散大脑区域中的前脑啡肽mRNA含量。与对照动物相比,慢性纳曲酮治疗 (8 d) 导致前脑啡肽前mRNA的纹状体含量增加了约12倍。相反,亲环蛋白 (1B15) 或肌动蛋白的纹状体mRNA未观察到统计学上的显着变化。前脑啡肽mRNA含量在海马 (+ 40%) 和下丘脑 (+ 19%) 中出现少量增加。额叶皮层无明显变化。早在拮抗剂治疗后24小时,就可以看到mRNA水平的升高。相比之下,慢性拮抗剂治疗后,阿片受体密度的变化需要3-4 d才能达到一半的最大上调。最近的证据表明,p物质受阿片肽调节。为了确定是否通过慢性拮抗剂治疗改变了p物质的合成,使用用于exon-7预速激肽基因的探针检查了对应于p物质前体的mRNA。与对照动物相比,慢性拮抗剂治疗后,纹状体中的促前激肽mRNA含量增加了6倍。慢性拮抗剂治疗后,p物质含量增加了3倍。这些数据表明,大脑阿片受体的慢性阻断导致纹状体中脑啡肽和p物质的合成增加,并且这些变化是相对特定的。(摘要截短于250字)

+1
+2
100研值 100研值 ¥99课程
检索文献一次
下载文献一次

去下载>

成功解锁2个技能,为你点赞

《SCI写作十大必备语法》
解决你的SCI语法难题!

技能熟练度+1

视频课《玩转文献检索》
让你成为检索达人!

恭喜完成新手挑战

手机微信扫一扫,添加好友领取

免费领《Endnote文献管理工具+教程》

微信扫码, 免费领取

手机登录

获取验证码
登录