Wang H Q, Kampine J P, Tseng L F
Department of Anesthesiology, Medical College of Wisconsin, Milwaukee 53226, USA.
Neuroscience. 1996 Nov;75(2):445-52. doi: 10.1016/0306-4522(96)00309-0.
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.
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。
