Ligand-induced μ opioid receptor internalization in enteric neurons following chronic treatment with the opiate fentanyl.
Ligand-induced μ opioid receptor internalization in enteric neurons following chronic treatment with the opiate fentanyl.
复制标题
DOI：
10.1002/jnr.23214
复制
发表时间：
2013-06
影响因子：
4.2
通讯作者：
Sternini, Catia
中科院分区：
文献类型：
--
作者：
Anselmi, Laura;Jaramillo, Ingrid;Palacios, Michelle;Huynh, Jennifer;Sternini, Catia
吗啡不同于大多数阿片类药物，因为它内化μ阿片受体(μOR)的能力很差。然而，长期使用吗啡可在动力素水平上产生适应性变化，从而提高急性吗啡刺激的效率，从而促进肠神经元内化μ或内化。本研究采用豚鼠回肠器官培养模型，研究了慢性应用μOR内化激动剂芬太尼对配体诱导的肠神经细胞内吞作用和细胞内转运蛋白Dynamin和çarrestin表达的影响。在长期使用芬太尼处理的豚鼠肠神经细胞中，μ或免疫反应主要出现在急性吗啡暴露后的细胞表面，μ或易位水平较低，略高于单纯动物的神经元。这种内化不是由于吗啡的直接作用，因为在单独暴露于介质的神经元中也观察到了这种内化。相反，D-丙氨酸-N-Me-苯基-甘氨酸-5-脑啡肽是一种有效的μOR内化激动剂，可在长期使用芬太尼的动物或幼稚动物的肠神经元中诱导显著而快速的μ或内吞作用。慢性芬太尼治疗不改变Dynamin或β-arrestin的表达。这些发现表明，用芬太尼等内化激动剂延长μOR的激活时间并不能增强急性吗啡触发μOR内吞作用的能力，也不会引起细胞内转运蛋白的变化，而用内化程度较差的吗啡等激动剂延长μOR的激活时间则不同。阿片类药物慢性处理诱导的细胞适应可能是配体依赖的，并随激动剂诱导受体内化的效率而变化。
Morphine differs from most opiates for its poor ability to internalize μ opioid receptors (μORs). However, chronic treatment with morphine produces adaptational changes at the dynamin level, which enhance the efficiency of acute morphine stimulation to promote μOR internalization in enteric neurons. This study tested the effect of chronic treatment with fentanyl, a μOR internalizing agonist, on ligand-induced endocytosis and the expression of the intracellular trafficking proteins, dynamin and ß arrestin, in enteric neurons using organotypic cultures of the guinea pig ileum. In enteric neurons from guinea pigs chronically treated with fentanyl, μOR immunoreactivity was predominantly at the cell surface following acute exposure to morphine with a low level of μOR translocation, slightly higher than in neurons from naïve animals. This internalization was not due to morphine direct effect because it was also observed in neurons exposed to medium alone. By contrast, D-Ala2-N-Me-Phe4-Gly-ol5-enkephalin (DAMGO), a potent μOR-internalizing agonist, induced pronounced and rapid μOR endocytosis in enteric neurons from animals chronically treated with fentanyl or from naïve animals. Chronic fentanyl treatment did not alter dynamin or β-arrestin expression. These findings indicate that prolonged activation of μORs with an internalizing agonist such as fentanyl does not enhance the ability of acute morphine to trigger μOR endocytosis nor induces changes in intracellular trafficking proteins, as observed with prolonged activation of μORs with a poorly internalizing agonist such as morphine. Cellular adaptations induced by opiate chronic treatment might be ligand dependent and vary with the agonist efficiency to induce receptor internalization.
登录
查看更多内容
影响因子：
11.8
作者：
Macia, Eric;Ehrlich, Marcelo;Kirchhausen, Tomas
通讯作者：
Kirchhausen, Tomas
影响因子：
2.5
作者：
Ho, A;Lievore, A;Sternini, C
通讯作者：
Sternini, C
影响因子：
64.8
作者：
Matthes, HWD;Maldonado, R;Kieffer, BL
通讯作者：
Kieffer, BL
影响因子：
5.3
作者：
Debic, HH;Kim, KA;von Zastrow, M
通讯作者：
von Zastrow, M
DOI：
10.1073/pnas.81.22.7253
发表时间：
1984-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
CHAVKIN, C;GOLDSTEIN, A
通讯作者：
GOLDSTEIN, A