Biochemical evidence for orphanin FQ/nociceptin receptor heterogeneity in mouse brain
Biochemical evidence for orphanin FQ/nociceptin receptor heterogeneity in mouse brain
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DOI：
10.1006/bbrc.1996.5867
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发表时间：
1997-01-13
影响因子：
3.1
通讯作者：
Pasternak, GW
中科院分区：
文献类型：
--
作者：
Mathis, JP;RyanMoro, J;Pasternak, GW
新近发现的孤啡肽FQ/伤害素(OFQ/N)是克隆的阿片受体家族中一个独特成员的内源性配体。对小鼠脑膜的饱和研究显示，在脑组织中具有较高(K-D 3.8 pm，B-max 31.6fmol/mg蛋白质)和较低(K-D 896 pm，B-max 233 fmol/mg蛋白质)亲和力位置的曲线Scatchard图，而在转基因CHO细胞中只有一个位置(K-D 36 pm)。竞争研究证实，OFQ/N对该地点具有很高的亲和力，但浅山坡表明存在异质性。传统的阿片类药物对这种受体的亲和力很差，OFQ/N及其片段不标记传统的阿片受体。在脑匀浆中，OFQ/N和OFQ/N(1-11)均抑制Forsklin刺激的cAMP积聚，IC50值为1 nM或更小，这一作用很容易被阿片类拮抗剂逆转。OFQ/N(1-7)活性很低。综上所述，这些研究表明，小鼠大脑中存在异质的、功能活跃的OFQ/N受体。(C)1997年学术出版社
A recently identified novel peptide, orphanin FQ/nociceptin (OFQ/N), is an endogenous ligand for a unique member of the cloned opioid receptor family. Saturation studies in mouse brain membranes reveal curvilinear Scatchard plots with both a higher (K-D 3.8 pM, B-max 31.6 fmol/mg protein) and a lower (K-D 896 pM, B-max 233 fmol/mg protein) affinity site in brain tissue, compared to only a single site in transfected CHO cells (K-D 36 pM). Competition studies confirm the high affinity of OFQ/N for this site, but shallow Hill slopes suggest heterogeneity. Traditional opioids have poor affinity for this receptor and OFQ/N and its fragments do not label traditional opioid receptors. In brain homogenates, both OFQ/N and OFQ/N(1-11) inhibit forskolin-stimulated camp accumulation with IC50 values of 1 nM or less, an action which is readily reversed by opioid antagonists. OFQ/N(1-7) shows little activity. Together, these studies suggest the presence of heterogeneous, functionally active OFQ/N receptors in mouse brain. (C) 1997 Academic Press