针对δ-阿片受体信使核糖核酸的反义寡脱氧核苷酸可选择性地阻断小鼠脑室内注射δ-阿片受体激动剂（而非μ-、ε-或κ-阿片受体激动剂）所诱导的镇痛作用。

Antisense oligodeoxynucleotide to a delta-opioid receptor messenger RNA selectively blocks the antinociception induced by intracerebroventricularly administered delta-, but not mu-, epsilon- or kappa-opioid receptor agonists in the mouse.

作者信息

Wang H Q, Kampine J P, Tseng L F

机构信息

Department of Anesthesiology, Medical College of Wisconsin, Milwaukee 53226, USA.

出版信息

Neuroscience. 1996 Nov;75(2):445-52. doi: 10.1016/0306-4522(96)00309-0.

DOI:10.1016/0306-4522(96)00309-0

PMID:8931008

Abstract

An antisense oligodeoxynucleotide to delta-opioid receptor messenger RNA was utilized to block the expression of mouse delta-opioid receptors for antinociception. The antinociception was measured by the tail-flick test in male ICR mice. Pretreatment with delta-antisense oligodeoxynucleotide (163 pmol) given intracerebroventricularly twice a day for one to four days produced a time-dependent inhibition of the tail-flick response induced by intracerebroventricularly administered (D-Ala2)deltorphin II (12.8 nmol). The (D-Ala2)deltorphin II-induced antinociception was significantly attenuated after three to four days of the delta-antisense oligodeoxynucleotide treatment, remained attenuated for two days and gradually recovered to the control level in four to 10 days after cessation of the pretreatment with delta-antisense oligodeoxynucleotide. Pretreatment with delta-antisense oligodeoxynucleotide (163 pmol) twice a day for four days markedly attenuated the antinociception induced by intracerebroventricularly administered (D-Ala2)deltorphin II and, to a lesser extent, by D-Pen2-D-Pen5-enkephalin and morphine, but not by (D-Ala2-MePhe4-Gly(ol)5)enkephalin, beta-endorphin or U50,488H. Mismatched oligodeoxynucleotide (163 pmol) was ineffective against the antinociception induced by these opioids. Our results provide the evidence that the cloned delta-opioid receptor is related to the pharmacologically classified delta 2-opioid receptor, and the antinociception induced by (D-Ala2)deltorphin II and, at least in part, by D-Pen2-D-Pen5-enkephalin and morphine given intracerebroventricularly is mediated by the stimulation of delta 2-opioid receptors. However, delta 2-opioid receptors are not involved in the antinociception induced by beta-endorphin, (D-Ala2-MePhe4-Gly(ol)5)enkephalin or U50,488H given intracerebroventricularly.

摘要

利用针对δ-阿片受体信使核糖核酸的反义寡脱氧核苷酸来阻断小鼠δ-阿片受体的表达以进行抗伤害感受研究。通过对雄性ICR小鼠进行甩尾试验来测定抗伤害感受。每天两次脑室内注射δ-反义寡脱氧核苷酸（163皮摩尔），持续一至四天，可对脑室内注射（D-Ala2）强啡肽II（12.8纳摩尔）诱导的甩尾反应产生时间依赖性抑制。在δ-反义寡脱氧核苷酸治疗三至四天后，（D-Ala2）强啡肽II诱导的抗伤害感受显著减弱，在停止用δ-反义寡脱氧核苷酸预处理后的两天内仍保持减弱状态，并在四至十天内逐渐恢复到对照水平。每天两次脑室内注射δ-反义寡脱氧核苷酸（163皮摩尔），持续四天，可显著减弱脑室内注射（D-Ala2）强啡肽II诱导的抗伤害感受，对D-Pen2-D-Pen5-脑啡肽和吗啡诱导的抗伤害感受也有一定程度的减弱作用，但对（D-Ala2-MePhe4-Gly(ol)5）脑啡肽、β-内啡肽或U50,488H诱导的抗伤害感受无影响。错配的寡脱氧核苷酸（163皮摩尔）对这些阿片类药物诱导的抗伤害感受无效。我们的结果提供了证据，表明克隆的δ-阿片受体与药理学分类的δ2-阿片受体相关，并且脑室内注射（D-Ala2）强啡肽II以及至少部分地由脑室内注射D-Pen2-D-Pen5-脑啡肽和吗啡诱导的抗伤害感受是由δ2-阿片受体的刺激介导的。然而，δ2-阿片受体不参与脑室内注射β-内啡肽、（D-Ala2-MePhe4-Gly(ol)5）脑啡肽或U50,488H诱导的抗伤害感受。