ORPHANIN-FQ - A NEUROPEPTIDE THAT ACTIVATES AN OPIOID-LIKE G-PROTEIN-COUPLED RECEPTOR
ORPHANIN-FQ - A NEUROPEPTIDE THAT ACTIVATES AN OPIOID-LIKE G-PROTEIN-COUPLED RECEPTOR
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DOI：
10.1126/science.270.5237.792
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发表时间：
1995-11-03
期刊：
影响因子：
56.9
通讯作者：
CIVELLI, O
中科院分区：
文献类型：
--
作者：
REINSCHEID, RK;NOTHACKER, HP;CIVELLI, O
从猪脑组织中鉴定并纯化了一种十七肽，作为孤儿异三聚体 GTP 结合蛋白（G 蛋白）偶联受体（LC132）的配体，该受体在序列上与阿片受体相似。这种肽，孤啡肽 FQ，具有类似于阿片肽的一级结构。纳摩尔浓度的孤啡肽 FQ 可抑制 LC132 转染细胞中毛喉素刺激的腺苷酸环化酶活性。这种抑制活性不受添加阿片类配体的影响，肽也不会激活阿片类受体。孤啡肽 FQ 以可饱和方式和高亲和力与其受体结合。当向小鼠脑室内注射时，孤啡肽 FQ 会导致运动活动减少，但在热板试验中不会引起镇痛。然而，该肽在甩尾试验中产生痛觉过敏。因此，孤啡肽 FQ 可能通过调节伤害感受和运动行为而充当大脑中的递质。
A heptadecapeptide was identified and purified from porcine brain tissue as a ligand for an orphan heterotrimeric GTP- binding protein (G protein)- coupled receptor (LC132) that is similar in sequence to opioid receptors. This peptide, orphanin FQ, has a primary structure reminiscent of that of opioid peptides. Nanomolar concentrations of orphanin FQ inhibited forskolin-stimulated adenylyl cyclase activity in cells transfected with LC132. This inhibitory activity was not affected by the addition of opioid ligands, nor did the peptide activate opioid receptors. Orphanin FQ bound to its receptor in a saturable manner and with high affinity. When injected intracerebroventricularly into mice, orphanin FQ caused a decrease in locomotor activity but did not induce analgesia in the hot-plate test. However, the peptide produced hyperalgesia in the tail-flick assay. Thus, orphanin FQ may act as a transmitter in the brain by modulating nociceptive and locomotor behavior.