RAPID ENDOCYTOSIS OF A G-PROTEIN-COUPLED RECEPTOR - SUBSTANCE-P-EVOKED INTERNALIZATION OF ITS RECEPTOR IN THE RAT STRIATUM IN-VIVO
RAPID ENDOCYTOSIS OF A G-PROTEIN-COUPLED RECEPTOR - SUBSTANCE-P-EVOKED INTERNALIZATION OF ITS RECEPTOR IN THE RAT STRIATUM IN-VIVO
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DOI：
10.1073/pnas.92.7.2622
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发表时间：
1995-03-28
影响因子：
11.1
通讯作者：
MAGGIO, JE
中科院分区：
文献类型：
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作者：
MANTYH, PW;ALLEN, CJ;MAGGIO, JE
对培养细胞的研究表明，激动剂诱导几种类型的G蛋白偶联受体进行内化。我们研究了这种现象在大鼠纹状体，使用P物质（SP）诱导的SP受体（SPR）的内化作为我们的模型系统。在麻醉大鼠单侧纹状体注射SP后1分钟内，注射区内近60%的SPR免疫反应神经元显示出SPR的大量内化-即，每个细胞体有20-200个SPR（+）内体，在树突内，SPR经历了从质膜到内体的显著易位，并且这些树突也经历了形态学重组，从直径相当均匀的结构改变为特征在于由细纤维连接的大的、肿胀的静脉曲张的结构，在细胞体和树突中，SPR（+）内体的数量在SP注射的60分钟内恢复到基线。显示大量内体SPR内化的神经元的数量取决于注射的SP的浓度，SP诱导的SPR内化被非肽类神经激肽1受体拮抗剂RP-67，580抑制。这些数据表明，在中枢神经系统在体内，SP诱导一个快速和广泛的SPR内化的细胞体和树突和树突的结构重组。这些结果表明，许多已在G蛋白偶联受体在体外转染的细胞系统的内化和回收的意见是适用于类似的事件发生在哺乳动物中枢神经系统在体内。
Studies on cultured cells have shown that agonists induce several types of G protein-coupled receptors to undergo internalization. We have investigated this phenomenon in rat striatum, using substance P (SP)-induced internalization of the SP receptor (SPR) as our model system. Within 1 min of a unilateral striatal injection of SP in the anesthetized rat, nearly 60% of the SPR-immunoreactive neurons within the injection zone display massive internalization of the SPR-i.e., 20-200 SPR(+) endosomes per cell body, Within the dendrites the SPR undergoes a striking translocation from the plasma membrane to endosomes, and these dendrites also undergo a morphological reorganization, changing from a structure of rather uniform diameter to one characterized by large, swollen varicosities connected by thin fibers, In both cell bodies and dendrites the number of SPR(+) endosomes returns to baseline within 60 min of SP injection, The number of neurons displaying substantial endosomal SPR internalization is dependent on the concentration of injected SP, and the SP-induced SPR internalization is inhibited by the nonpeptide neurokinin 1 receptor antagonist RP-67,580. These data demonstrate that in the central nervous system in vivo, SP induces a rapid and widespread SPR internalization in the cell bodies and dendrites and a structural reorganization of the dendrites. These results suggest that many of the observations that have been made on the internalization and recycling of G protein-coupled receptors in in vitro transfected cell systems are applicable to similar events that occur in the mammalian central nervous system in vivo.