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人类脊髓中的神经降压素受体:一项定量放射自显影研究。

Neurotensin receptors in the human spinal cord: a quantitative autoradiographic study.

作者信息

Faull R L, Villiger J W, Dragunow M

机构信息

Department of Anatomy, School of Medicine, University of Auckland, New Zealand.

出版信息

Neuroscience. 1989;29(3):603-13. doi: 10.1016/0306-4522(89)90134-6.

Abstract

The anatomical localization of neurotensin receptors in the human spinal cord was examined in 12 cases aged 4-68 years using quantitative autoradiographic methods following the incubation of fresh, unfixed cryostat sections with 4 nM [3H]neurotensin. Characterization of the pharmacological specificity of the [3H]neurotensin binding sites in the human spinal cord from displacement studies with neurotensin and various neurotensin fragments indicated that, whereas 1.0 microM neurotensin and the carboxy-terminal fragment neurotensin almost completely displaced [3H]neurotensin binding (4 nM), the amino-terminal fragments neurotensin and neurotensin1-11 were weak inhibitors. This requirement for the carboxy-terminal fragment neurotensin is consistent with [3H]neurotensin binding to specific neurotensin receptors in the human spinal cord. In all cases the autoradiograms demonstrated that neurotensin receptors were distributed in a similar fashion in the gray matter of the cervical, thoracic, lumbar, sacral and coccygeal regions of the human spinal cord. At all 21 spinal levels examined, the highest density of neurotensin receptors was localized in lamina II of the dorsal horn. Within lamina II the receptors were especially concentrated in the deeper inner segment (IIi) where they formed a dense band lying immediately dorsal to lamina III. The density of receptors in this inner region of lamina II (23.5 fmol/mg) was almost double that in the outer segment of lamina II (12.2 fmol/mg), which showed the next highest density of receptors, and more than three times that in the adjacent lamina I (6.9 fmol/mg) and lamina III (7.1 fmol/mg). A moderate density of receptors was present in the intermediomedial (8.0 fmol/mg) and intermediolateral (8.0 fmol/mg) nuclei of lamina VII, and in lamina IX (4.4 fmol/mg). The density of labelling in the remaining laminae of the spinal cord was very low. These results indicate that neurotensin receptors are mainly localized in somatic and visceral sensory and motor regions of the human spinal cord and suggest that neurotensin may play a role in modulating sensory-motor functions in the human spinal cord.

摘要

采用定量放射自显影方法,用4 nM [³H]神经降压素孵育12例年龄在4至68岁的新鲜、未固定的冰冻切片后,研究了神经降压素受体在人脊髓中的解剖定位。通过用神经降压素和各种神经降压素片段进行置换研究,对人脊髓中[³H]神经降压素结合位点的药理学特异性进行了表征,结果表明,虽然1.0 μM神经降压素和羧基末端片段神经降压素几乎完全置换了[³H]神经降压素结合(4 nM),但氨基末端片段神经降压素和神经降压素1 - 11是弱抑制剂。对羧基末端片段神经降压素的这种需求与[³H]神经降压素与人脊髓中特定神经降压素受体的结合一致。在所有病例中,放射自显影片显示神经降压素受体在人脊髓颈、胸、腰、骶和尾段灰质中的分布方式相似。在所检查的所有21个脊髓节段中,神经降压素受体的最高密度位于背角的Ⅱ层。在Ⅱ层内,受体特别集中在较深的内侧段(Ⅱi),在那里它们形成一条紧位于Ⅲ层背侧的致密带。Ⅱ层内侧区域的受体密度(23.5 fmol/mg)几乎是Ⅱ层外侧段(12.2 fmol/mg)的两倍,Ⅱ层外侧段显示出第二高的受体密度,是相邻的Ⅰ层(6.9 fmol/mg)和Ⅲ层(7.1 fmol/mg)的三倍多。Ⅶ层的中间内侧核(8.0 fmol/mg)和中间外侧核(8.0 fmol/mg)以及Ⅸ层(4.4 fmol/mg)存在中等密度的受体。脊髓其余层的标记密度非常低。这些结果表明神经降压素受体主要定位于人脊髓的躯体和内脏感觉及运动区域,并提示神经降压素可能在调节人脊髓的感觉运动功能中发挥作用。

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