Identification of the receptor subtype involved in the analgesic effect of neurotensin
Identification of the receptor subtype involved in the analgesic effect of neurotensin
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DOI：
10.1523/jneurosci.19-01-00503.1999
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发表时间：
1999-01-01
影响因子：
5.3
通讯作者：
Mazella, J
中科院分区：
文献类型：
--
作者：
Dubuc, I;Sarret, P;Mazella, J
脑注射神经肽神经降压素（NT）后引起低温和纳洛酮不敏感的镇痛反应。最近的药理学证据表明，这些作用是由一个受体介导的，不同于最初克隆的高亲和力MT受体（NTR 1），最近克隆的第二个NT受体（NTR 2）促使我们评估其在NT诱导的镇痛作用。侧脑室注射两种不同的反义寡核苷酸从NTR 2的小鼠显着降低NTR 2的mRNA和蛋白，减少NT诱导的镇痛。这种效应是特异性的，因为NTR 1水平不受影响，正义或混乱寡脱氧核苷酸没有影响。结构-活性研究揭示了NT类似物的镇痛效力与其对NTR 2的亲和力之间的密切相关性，并公开了该受体的有效和选择性激动剂。这些数据证实NTR 1参与NT引起的转向行为，并证明NTR 2介导NT引起的镇痛。
The neuropeptide neurotensin (NT) elicits hypothermic and naloxone-insensitive analgesic responses after brain injection. Recent pharmacological evidence obtained with NT agonists and antagonists suggests that these effects are mediated by a receptor distinct from the initially cloned high-affinity MT receptor (NTR1), The recent cloning of a second NT receptor (NTR2) prompted us to evaluate its role in NT-induced analgesia. Intracerebroventricular injections in mice of two different antisense oligodeoxynucleotides from the NTR2 markedly decreased NTR2 mRNA and protein and reduced NT-induced analgesia. This effect was specific, because NTR1 levels were unaffected, and sense or scramble oligodeoxynucleotides had no effect. Structure-activity studies revealed a close correlation between the analgesic potency of NT analogs and their affinity for the NTR2 and disclosed potent and selective agonists of this receptor. These data confirm that NTR1 is involved in the NT-elicited turning behavior and demonstrate that the NTR2 mediates NT-induced analgesia.