Distribution of ecto-nucleotidases in mouse sensory circuits suggests roles for nucleoside triphosphate diphosphohydrolase-3 in nociception and mechanoreception.
Distribution of ecto-nucleotidases in mouse sensory circuits suggests roles for nucleoside triphosphate diphosphohydrolase-3 in nociception and mechanoreception.
复制标题
DOI：
10.1016/j.neuroscience.2011.07.044
复制
发表时间：
2011-10-13
期刊：
影响因子：
3.3
通讯作者：
Molliver, D. C.
中科院分区：
文献类型：
--
作者：
Vongtau, H. O.;Lavoie, E. G.;Sevigny, J.;Molliver, D. C.
核苷酸激活的P2X通道和P2Y代谢受体参与伤害性信号传导。激动剂的可用性受三磷酸核苷二磷酸水解酶-1 (ntpase) -1、-2、-3和-8的调控，这是一个酶家族，可水解细胞外ATP生成二磷酸腺苷（ADP，一种P2Y激动剂）和一磷酸腺苷（AMP）。它们是细胞外AMP的主要来源，AMP是胞外5′-核苷酸酶（NT5E）产生腺苷的底物，从而调节腺苷（P1）受体信号传导。ntpase的三磷酸和二磷酸水解效率不同；因此，哪些家族成员被表达影响核苷酸的可用性和半衰期。本研究采用酶活性组织化学方法检测ATPase活性的分布以及ntpase 1、-2、-3和-8在背根神经节（DRG）和脊髓中的免疫组织化学表达。脊髓背角的核苷酸酶活性强劲，证实伤害性通路是核苷酸传递的主要部位。在DRG中，广泛染色显示神经元亚群和非神经元细胞中有atp酶活性。在腰椎DRG和脊髓中检测到NTPDase1-3的mRNA，但未检测到NTPDase8的mRNA。NTPDase3的免疫反应性与ATPase活性的分布密切匹配，标记了DRG在背根和浅表背角的中央投射，以及集中在II层的固有脊髓神经元。在DRG中，NTPDase3与伤害感受器标记物和NT5E共定位。此外，DRG中大直径神经元亚群的标记与无毛皮肤中迈斯纳小体传入的强染色一致。毛囊传入神经的梅克尔细胞和终末雪旺细胞也被标记，但轴突本身为阴性。我们认为NTPDase3是伤害性信号的关键调节因子，也对无害的触觉产生意想不到的影响。
Nucleotide-activated P2X channels and P2Y metabotropic receptors participate in nociceptive signaling. Agonist availability is regulated by nucleoside triphosphate diphosphohydrolase-1 (NTPDase) -1, -2, -3 and -8, a family of enzymes that hydrolyze extracellular ATP to generate adenosine diphosphate (ADP, a P2Y agonist) and monophosphate (AMP). They provide a major source of extracellular AMP, the substrate for adenosine production by ecto-5′-nucleotidase (NT5E), and thereby regulate adenosine (P1) receptor signaling. NTPDases vary in their efficiency of tri- and di-phosphate hydrolysis; therefore which family members are expressed impacts nucleotide availability and half-life. This study employed enzyme activity histochemistry to examine the distribution of ATPase activity and immunohistochemistry for NTPDase1, -2, -3 and -8 in dorsal root ganglion (DRG) and spinal cord. Nucleotidase activity was robust in spinal dorsal horn, confirming that nociceptive pathways are a major site of nucleotide transmission. In DRG, extensive staining revealed ATPase activity in a subset of neurons and in non-neuronal cells. mRNA for NTPDase1-3, but not NTPDase8, was detected in lumbar DRG and spinal cord. Immunoreactivity for NTPDase3 closely matched the distribution of ATPase activity, labeling DRG central projections in the dorsal root and superficial dorsal horn, as well as intrinsic spinal neurons concentrated in lamina II. In DRG, NTPDase3 co-localized with markers of nociceptors and with NT5E. In addition, labeling of a subset of larger-diameter neurons in DRG was consistent with intense staining of Meissner corpuscle afferents in glabrous skin. Merkel cells and terminal Schwann cells of hair follicle afferents were also labeled, but the axons themselves were negative. We propose that NTPDase3 is a key regulator of nociceptive signaling that also makes an unexpected contribution to innocuous tactile sensation.
登录
查看更多内容
影响因子：
10.8
作者：
Kauffenstein, Gilles;Drouin, Annick;Sevigny, Jean
通讯作者：
Sevigny, Jean
影响因子：
2.5
作者：
HALATA, Z;MUNGER, BL
通讯作者：
MUNGER, BL
影响因子：
6.5
作者：
Denda, M;Inoue, K;Denda, S
通讯作者：
Denda, S
影响因子：
3.4
作者：
Braun, N;Sévigny, J;Zimmermann, H
通讯作者：
Zimmermann, H
影响因子：
7.3
作者：
Communi, D;Robaye, B;Boeynaems, JM
通讯作者：
Boeynaems, JM