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生长抑素受体在正常和单关节炎大鼠背根神经节神经元中的表达与定位

The expression and localization of somatostatin receptors in dorsal root ganglion neurons of normal and monoarthritic rats.

作者信息

Bär K-J, Schurigt U, Scholze A, Segond Von Banchet G, Stopfel N, Bräuer R, Halbhuber K-J, Schaible H-G

机构信息

Klinik für Psychiatrie, Friedrich-Schiller-Universität Jena, Philosophenweg 3, D-07740 Jena, Germany.

出版信息

Neuroscience. 2004;127(1):197-206. doi: 10.1016/j.neuroscience.2004.04.051.

Abstract

Somatostatin has antinociceptive effects by acting on somatostatin (sst) receptors in primary afferent neurons. Five sst receptor subtypes (sst(1-5)) have been identified. In the present study we assessed the expression and localization of the sst receptor subtypes in lumbar dorsal root ganglia of normal rats and of rats with unilateral antigen-induced arthritis (AIA) in the knee joint. We used polymerase chain reaction (PCR) of material from dorsal root ganglia and immunohistochemistry in dorsal root ganglion paraffin sections. PCR data show that sst(1), sst(2(a)), sst(2(b)), sst(3), and sst(4) receptors are expressed in lumbar dorsal root ganglia of the rat. The sst(5) receptor was expressed in a few samples. Available antibodies revealed sst(2(a)) and sst(2(b)) receptor-like immunoreactivity in the vast majority of neurons, and sst(4) receptor-like immunoreactivity in about 40% of the dorsal root ganglion neurons and in some satellite cells. Real time PCR at 3, 10 and 21 days after induction of AIA did not reveal changes in receptor expression. Immunohistochemistry showed that a similar high proportion of neuronal profiles expressed sst(2(b)) receptor-like IR in control and AIA rats, but the proportion of neuronal profiles with sst(2(a)) receptor-like IR was significantly lower in acute and chronic AIA rats than in control rats. Although the proportion of neuronal profiles with sst(4) receptor-like IR was significantly higher at 21 days than at 3 days values at 3 or at 21 days were not significantly different from control. These data show that the majority of dorsal root ganglion neurons exhibit somatostatin receptor-like IR thus suggesting a high potential for inhibition by somatostatin. The reduction in the proportion of neuronal profiles with sst(2(a)) immunoreactivity suggests that inhibition of neuronal activity by somatostatin is reduced during painful arthritis.

摘要

生长抑素通过作用于初级传入神经元中的生长抑素(sst)受体发挥抗伤害感受作用。已鉴定出五种sst受体亚型(sst(1 - 5))。在本研究中,我们评估了正常大鼠以及膝关节单侧抗原诱导性关节炎(AIA)大鼠腰段背根神经节中sst受体亚型的表达和定位。我们采用背根神经节材料的聚合酶链反应(PCR)以及背根神经节石蜡切片的免疫组织化学方法。PCR数据显示,sst(1)、sst(2(a))、sst(2(b))、sst(3)和sst(4)受体在大鼠腰段背根神经节中表达。sst(5)受体在少数样本中表达。现有抗体显示,绝大多数神经元中有sst(2(a))和sst(2(b))受体样免疫反应性,约40%的背根神经节神经元和一些卫星细胞中有sst(4)受体样免疫反应性。AIA诱导后3天、10天和21天的实时PCR未显示受体表达的变化。免疫组织化学显示,对照组和AIA大鼠中,表达sst(2(b))受体样免疫反应性的神经元轮廓比例相似,但急性和慢性AIA大鼠中具有sst(2(a))受体样免疫反应性的神经元轮廓比例显著低于对照组大鼠。尽管具有sst(4)受体样免疫反应性的神经元轮廓比例在21天时显著高于3天时,但3天或21天时的值与对照组无显著差异。这些数据表明,大多数背根神经节神经元表现出生长抑素受体样免疫反应性,因此提示生长抑素具有较高的抑制潜力。具有sst(2(a))免疫反应性的神经元轮廓比例降低表明,在疼痛性关节炎期间,生长抑素对神经元活动的抑制作用减弱。

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