人类型阿片受体机制agonist-induced下调:内化需要下调。
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李詹,Benovic杰,刘晨LY
人类型阿片受体机制agonist-induced下调:内化需要下调。
摩尔杂志。2000年10月,58 (4):795 - 801。
- PubMed ID
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10999950 (在PubMed]
- 文摘
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以前,我们表明,人类型阿片受体(hkor)稳定表达的中国仓鼠卵巢(CHO)细胞长期U50,488H治疗后进行了下调。在目前的研究中,我们确定了机制这一过程。U50, 488 h hkor造成显著下调,尽管埃托啡没有。无论是U50,488H还是埃托啡导致老鼠型阿片受体下调。因此,类似于内部化,有兴奋剂和物种差异型阿片受体下调。表达的显性负突变体arrestin-2(319 - 418)或dynamin I-K44A显著降低U50,488H-induced hkor的下调。Coexpression GRK2或GRK2 arrestin-2允许埃托啡诱导hkor下调,尽管表达arrestin-2或者dynamin我独自一人没有。表达的显性负突变体rab5A-N133I或rab7-N125I钝化U50,488H-induced下调。与溶酶体酶抑制剂预处理[(2 s, 3 s) trans-epoxysuccinyl-L-leucylamido-3-methylbutane乙酯或氯喹)或蛋白酶体抑制剂(蛋白酶体抑制剂,mg - 132,或lactacystin)下降的程度U50,488H-induced下调。氯喹和蛋白酶体抑制剂我废除U50,488H-induced下调。 These results indicate that U50,488H-induced down-regulation of the hkor involves GRK-, arrestin-2-, dynamin-, rab5-, and rab7-dependent mechanisms and receptors seem to be trafficked to lysosomes and proteasomes for degradation. Thus, U50,488H-induced internalization and down-regulation of the hkor share initial common mechanisms. To the best of our knowledge, these results represent the first report on the involvement of both rab5 and rab7 in agonist-induced down-regulation of a G protein-coupled receptor. In addition, this study is among the first to show the involvement of proteasomes in agonist-induced down-regulation of a G protein-coupled receptor.