Endomorphin-stimulated [35S]GTPgammaS binding in rat brain: evidence for partial agonist activity at mu-opioid receptors.
Endomorphin-stimulated [35S]GTPgammaS binding in rat brain: evidence for partial agonist activity at mu-opioid receptors.
复制标题
大鼠脑中内吗啡刺激的 [35S]GTPgammaS 结合：mu-阿片受体部分激动剂活性的证据。
DOI：
10.1046/j.1471-4159.1998.70041567.x
复制
发表时间：
1998
影响因子：
4.7
通讯作者：
Selley,DE
中科院分区：
文献类型：
--
作者：
Sim,LJ;Liu,Q;Childers,SR;Selley,DE
Endomorphin‐1 is a peptide whose binding selectivity suggests a role as an endogenous ligand at μ‐opioid receptors. In the present study, the effect of endomorphin‐1 on μ receptor‐coupled G proteins was compared with that of the μ agonist DAMGO by using agonist‐stimulated [35S]GTPγS binding in rat brain. [35S]GTPγS autoradiography revealed a similar localization of endomorphin‐1 and DAMGO‐stimulated [35S]GTPγS binding in areas including thalamus, caudate‐putamen, amygdala, periaqueductal gray, parabrachial nucleus, and nucleus tractus solitarius. Naloxone blocked endomorphin‐1‐stimulated labeling in all regions examined. Although the distribution of endomorphin‐1‐stimulated [35S]GTPγS binding resembled that of DAMGO, the magnitude of endomorphin‐1‐stimulated binding was significantly lower than that produced by DAMGO. Concentration‐effect curves of endomorphin‐1 and DAMGO in thalamic membranes confirmed that endomorphin‐1 produced only 70% of DAMGO‐stimulated [35S]GTPγS binding. Differences in maximal stimulation of [35S]GTPγS binding between DAMGO and endomorphin‐1 were magnified by increasing GDP concentrations, and saturation analysis of net endomorphin‐1‐stimulated [35S]GTPγS binding revealed a lower apparentBmaxvalue than that obtained with DAMGO. Endomorphin‐1 also partially antagonized DAMGO stimulation of [35S]GTPγS binding. These results demonstrate that endomorphin‐1 is a partial agonist for G protein activation at the μ‐opioid receptor in brain.
