Raffa R B, Martinez R P, Connelly C D
R.W. Johnson Pharmaceutical Research Institute, Spring House, PA 19477-0776.
Eur J Pharmacol. 1994 Jun 2;258(1-2):R5-7. doi: 10.1016/0014-2999(94)90073-6.
The present study utilized an in vivo antisense strategy to examine the functional interaction of supraspinal mu-opioid receptors with the G protein subunits Gi1 alpha, Gi2 alpha, Gi3 alpha and Gs alpha. Mice were injected intracerebroventricularly (i.c.v.) with 33-base phosphorothioate oligodeoxyribonucleotides (12.5 micrograms) or with vehicle in equal volume (sterile water, 5 microliters) and the antinociceptive responses to i.c.v. morphine [D-Ala2,NMePhe4,Gly5-ol]enkephalin (DAMGO) or sufentanil were determined 18-24 h later using the tail-flick test. Treatment with antisense to Gi2 alpha, but not the other subunits, significantly attenuated morphine-induced antinociception. The degree of attenuation for the three mu-opioid agonists was in the order morphine > DAMGO > sufentanil, the inverse of their intrinsic efficacy.
本研究采用体内反义策略，以检验脊髓上μ-阿片受体与G蛋白亚基Gi1α、Gi2α、Gi3α和Gsα之间的功能相互作用。给小鼠脑室内（i.c.v.）注射33个碱基的硫代磷酸酯寡脱氧核糖核苷酸（12.5微克）或等体积的溶剂（无菌水，5微升），并在18 - 24小时后使用甩尾试验测定对i.c.v.吗啡、[D-Ala2，NMePhe4，Gly5-ol]脑啡肽（DAMGO）或舒芬太尼的抗伤害感受反应。用针对Gi2α而非其他亚基的反义寡核苷酸处理，可显著减弱吗啡诱导的抗伤害感受作用。三种μ-阿片激动剂的减弱程度顺序为吗啡>DAMGO>舒芬太尼，与其内在效能相反。
