Rossi G, Pan Y X, Cheng J, Pasternak G W
Cotzias Laboratory of Neuro-Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021.
Life Sci. 1994;54(21):PL375-9. doi: 10.1016/0024-3205(94)90038-8.
The recent cloning of mu, delta and kappa 1 opioid receptors has provide opportunities in the study of their pharmacology. Using an antisense strategy developed against delta and kappa 1 opioid receptors, we designed an antisense oligodeoxynucleotide directed against the 5'-untranslated region of MOR-1 clone, 51-70 bp upstream from the initiating ATG. Microinjection of this antisense oligodeoxynucleotide directly into the periaqueductal gray on Days 1, 3 and 5 completely blocked the analgesic actions of morphine administered into the periaqueductal gray on Day 6 (p < 0.001), 24 hr after the last antisense treatment. Rats treated with vehicle or with a mismatch oligodeoxynucleotide in which two pairs of bases from the antisense sequence had been switched were not significantly affected. These findings confirm the pharmacological relevance of the MOR-1 clone and its involvement in morphine's actions.
近期μ、δ和κ1阿片受体的克隆为其药理学研究提供了契机。利用针对δ和κ1阿片受体开发的反义策略，我们设计了一种反义寡脱氧核苷酸，它靶向MOR-1克隆5'-非翻译区，位于起始ATG上游51 - 70个碱基对处。在第1、3和5天，将这种反义寡脱氧核苷酸直接显微注射到导水管周围灰质中，在最后一次反义治疗24小时后的第6天，完全阻断了向导水管周围灰质注射吗啡的镇痛作用（p < 0.001）。用载体或用错配寡脱氧核苷酸（其中反义序列的两对碱基已被替换）处理的大鼠未受到显著影响。这些发现证实了MOR-1克隆的药理学相关性及其参与吗啡作用的过程。
