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首页> 外文期刊>DNA and Cell Biology >Recycling and Resensitization of Delta Opioid Receptors
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Recycling and Resensitization of Delta Opioid Receptors

机译：阿片类阿片受体的回收和再敏化

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Exposure to opioids results in the activation of opioid receptors; this is followed by receptor endocytosis. Previously, we showed that delta opioid receptors undergo rapid agonist-mediated internalization and that mutations in the C-tail result in a substantial loss of agonist-mediated internalization. In this study, we investigated the fate of receptors following rapid internalization. We found that the majority of the wild type receptors recycled back to the surface after acute agonist treatment. The kinetics of internalization and recycling of the receptor were virtually identical to the kinetics of internalization and recycling of the radiolabeled agonist. In contrast, the kinetics of internalization and recycling of a C-tail mutant receptor were substantially altered, suggesting an involvement of the C-tail in the recycling process. It is possible that in addition to agonist-mediated internalization, opioid receptors undergo constitutive, agonist-independent internalization. We directly examined this possibility using an antibody-prebinding assay. The wild type delta opioid receptors exhibited agonist-independent internalization via the clathrin-coated pit pathway. We also examined the role of receptor internalization and recycling in the modulation of its function by quantitating the level of opioid-stimulated phosphorylation of MAP kinase (MAPK) under conditions of receptor internalization and recycling. We found that agonist treatment caused a rapid increase in the level of phosphorylated MAPK that was rapidly desensitized. The removal of the agonist, which results in receptor recycling, led to the resensitization of the receptor, as evidenced by the agonist’s ability to reinduce MAPK phosphorylation. Mutant receptors that underwent rapid recycling exhibited enhanced resensitization, suggesting a role for receptor recycling in the resensitization process. Taken together, these results indicate that agonist-mediated internalization and recycling modulate opioid receptor function and that the receptor C-tail plays an important role in both processes.
机译：暴露于阿片类药物会导致阿片受体的活化。其次是受体的内吞作用。以前，我们表明，δ阿片受体经历了快速的激动剂介导的内化作用，C尾突变导致激动剂介导的内化作用大量丧失。在这项研究中，我们调查了快速内在化后受体的命运。我们发现，大多数野生型受体在急性激动剂治疗后再循环回到表面。受体的内在化和再循环的动力学实际上与放射性标记激动剂的内在化和再循环的动力学相同。相反，C-尾突变体受体的内在化和再循环的动力学被显着改变，表明C-尾参与了再循环过程。除了激动剂介导的内化作用外，阿片受体还可能经历组成型，与激动剂无关的内化作用。我们使用抗体预结合测定法直接检查了这种可能性。野生型δ阿片样物质受体通过网格蛋白涂层的坑途径表现出独立于激动剂的内在化。我们还通过量化受体内在化和再循环条件下阿片类药物刺激的MAP激酶（MAPK）的磷酸化水平来检查受体内在化和再循环在调节其功能中的作用。我们发现激动剂治疗引起迅速脱敏的磷酸化MAPK水平的迅速增加。激动剂的去除导致受体回收，导致受体重新敏化，激动剂重新诱导MAPK磷酸化的能力证明了这一点。经历快速再循环的突变受体表现出增强的再敏化，表明受体在再敏化过程中再循环的作用。综上所述，这些结果表明激动剂介导的内在化和再循环调节阿片样物质受体功能，并且受体C-尾在这两个过程中均起重要作用。

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