吗啡、DAMGO和内吗啡肽I引起的特定G蛋白激活及μ-阿片受体内化。
Specific G protein activation and mu-opioid receptor internalization caused by morphine, DAMGO and endomorphin I.
作者信息
Burford N T, Tolbert L M, Sadee W
机构信息
Department of Biopharmaceutical Sciences and Pharmaceutical Chemistry, University of California, San Francisco 94143-0446, USA.
出版信息
Eur J Pharmacol. 1998 Jan 19;342(1):123-6. doi: 10.1016/s0014-2999(97)01556-2.
Previous studies have shown that the agonist [D-Ala2, N-Me-Phe4, Gly-ol5]enkephalin (DAMGO) but not morphine induces mu-opioid receptor internalization [Arden, J.R., Segredo, V., Wang, Z., Lameh, J., Sadee, W., 1995. J. Neurochem. 65, 1636-1645]. In the present study we investigated the relationship between internalization of the mu-opioid receptor and the specific G proteins activated following treatment with morphine, DAMGO and endomorphin I (Tyr-Pro-Trp-Phe-NH2) (a putative endogenous mu-opioid receptor agonist) in human embryonic kidney (HEK) cells. Endomorphin I and DAMGO, but not morphine, caused mu-opioid receptor internalization. Morphine, DAMGO and endomorphin I each activated Gi1 alpha/Gi2 alpha, Go alpha and Gi3 alpha to a similar extent, but not Gq alpha/G11 alpha or Gs alpha in HEK membranes. Therefore, the three ligands tested differed in their ability to internalize mu-opioid receptors even though they were similar in activating individual G proteins.
先前的研究表明，激动剂[D-丙氨酸2，N-甲基苯丙氨酸4，甘氨酸醇5]脑啡肽（DAMGO）而非吗啡可诱导μ-阿片受体内化[阿登，J.R.，塞格雷多，V.，王，Z.，拉梅，J.，萨迪，W.，1995年。《神经化学杂志》65，1636 - 1645]。在本研究中，我们调查了在人胚肾（HEK）细胞中，μ-阿片受体内化与用吗啡、DAMGO和内吗啡肽I（酪氨酸-脯氨酸-色氨酸-苯丙氨酸-氨基）（一种假定的内源性μ-阿片受体激动剂）处理后激活的特定G蛋白之间的关系。内吗啡肽I和DAMGO可导致μ-阿片受体内化，而吗啡则不能。吗啡、DAMGO和内吗啡肽I在HEK细胞膜中对Gi1α/Gi2α、Goα和Gi3α的激活程度相似，但对Gqα/G11α或Gsα无激活作用。因此，所测试的三种配体在诱导μ-阿片受体内化的能力上存在差异，尽管它们在激活单个G蛋白方面相似。
Zotero 插件