Regulation of nociceptive neurons by nerve growth factor and glial cell line derived neurotrophic factor

Regulation of nociceptive neurons by nerve growth factor and glial cell line derived neurotrophic factor
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DOI:
10.1139/y02-034
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发表时间:
2002-05-01
影响因子:
2.1
通讯作者:
Willmott, N
Willmott, N
中科院分区:
医学4区
文献类型:
--
作者:
Priestley, JV;Michael, GJ;Willmott, N

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伤害性背根神经节(DRG)细胞可分为三个主要群体,即(1)小直径非肽表达细胞,(2)小直径肽表达(降钙素基因相关肽(CGRP),P物质)细胞,和(3)中等直径肽表达(CGRP)细胞。这些细胞群的属性将进行审查,特别强调的香草素(辣椒素)受体VR1的表达和生长因子的调节。群体1和2中的细胞表达VR1,VR1是一种非选择性通道,其转导某些伤害性刺激,并且对多模态伤害感受器的功能至关重要。细胞群1中的细胞可由胶质细胞系衍生的神经营养因子(GDNF)调节,而细胞群2和3中的细胞可由神经生长因子(NGF)调节。在体内,DRG细胞表达一系列水平的VR1表达,并且VR1在轴突切断后下调。然而,用NGF或GDNF治疗可以防止这种下调。在体外,DRG细胞也显示出一系列的神经生长因子和(或)GDNF依赖的VR1表达水平。功能研究表明,新鲜分离的细胞也显示出对辣椒素敏感性的差异。其意义尚不清楚,但可能表明细胞群1和2中细胞的生理作用存在差异。
Nociceptive dorsal root ganglion (DRG) cells can be divided into three main populations, namely (1) small diameter non-peptide-expressing cells, (2) small-diameter peptide-expressing (calcitonin gene related peptide (CGRP), substance P) cells, and (3) medium-diameter peptide-expressing (CGRP) cells. The properties of these cell populations will be reviewed, with a special emphasis on the expression of the vanilloid (capsaicin) receptor VR1 and its regulation by growth factors. Cells in populations 1 and 2 express VR1, a nonselective channel that transduces certain nociceptive stimuli and that is crucial to the functioning of polymodal nociceptors. Cells in population 1 can be regulated by glial cell line derived neurotrophic factor (GDNF) and those in populations 2 and 3 by nerve growth factor (NGF). In vivo, DRG cells express a range of levels of VR1 expression and VR1 is downregulated after axotomy. However, treatment with NGF or GDNF can prevent this downregulation. In vitro, DRG cells also show a range of VR1 expression levels that is NGF and (or) GDNF dependent. Functional studies indicate that freshly dissociated cells also show differences in sensitivity to capsaicin. The significance of this is not known but may indicate a difference in the physiological role of cells in populations 1 and 2.