Park Y, Ma T, Tanaka S, Jang C, Loh H H, Ko K H, Ho I K
Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, MS 32916-4505, USA.
Brain Res Bull. 2000 Jul 1;52(4):297-302. doi: 10.1016/s0361-9230(00)00265-3.
Mice lacking the mu-opioid receptor gene have been developed by a gene knockout procedure. In this study, the activity of opioid receptor coupled G-proteins was examined to investigate whether there is a change in the extent of coupling for mu, delta-, and kappa-opioid receptors in mu-opioid receptor knockout mice. Selective agonists of mu- (DAMGO), delta- (DPDPE), and kappa- (U-69,593) opioid receptors stimulated [(35)S]GTPgammaS binding in the caudate putamen and cortex of wild-type mice. In contrast, only U-69,593 stimulated [(35)S]GTPgammaS binding in these regions of mu-opioid receptor knockout mice. These results confirmed the absence of G-protein activation by a mu-opioid receptor agonist in mu-opioid receptor knockout mice, and demonstrated that coupling of the kappa-opioid receptor to G-proteins is preserved in these mice. However, G-protein activation by the delta-opioid receptor agonist, DPDPE, was reduced in the mu-opioid receptor knockout mice, at least in the brain regions studied using autoradiography.
通过基因敲除程序培育出了缺乏μ-阿片受体基因的小鼠。在本研究中，检测了阿片受体偶联G蛋白的活性，以研究μ-阿片受体基因敲除小鼠中μ、δ和κ阿片受体的偶联程度是否发生变化。μ-（DAMGO）、δ-（DPDPE）和κ-（U-69,593）阿片受体的选择性激动剂刺激了野生型小鼠尾壳核和皮质中的[³⁵S]GTPγS结合。相比之下，只有U-69,593刺激了μ-阿片受体基因敲除小鼠这些区域中的[³⁵S]GTPγS结合。这些结果证实了μ-阿片受体基因敲除小鼠中μ-阿片受体激动剂不会激活G蛋白，并表明κ-阿片受体与G蛋白的偶联在这些小鼠中得以保留。然而，至少在使用放射自显影术研究的脑区中，δ-阿片受体激动剂DPDPE对G蛋白的激活在μ-阿片受体基因敲除小鼠中有所减少。
