Shughrue Paul J, Ky Betty, Austin Christopher P
Department of Neuroscience, Merck Research Laboratories, Sumneytown Pike and Broad Street, WP26A-3000, West Point, PA 19486, USA.
J Comp Neurol. 2003 Oct 20;465(3):372-84. doi: 10.1002/cne.10846.
The bradykinin 1 and 2 receptors (B1R, B2R) are important mediators of cardiovascular homeostasis, inflammation, and nociception. While B2R is constitutively expressed in many tissues, B1R expression is thought to be absent, but induced under proinflammatory conditions. However, recent data from knockout mice have indicated that B1R acts centrally to mediate nociception, a finding that suggests the constitutive presence of B1R in brain and/or spinal cord. The purpose of the present study was to further elucidate the physiological role of B1R by evaluating the localization of B1R mRNA in the nonhuman primate brain and spinal cord with in situ hybridization. Cryostat sections from monkey brain and spinal cord were hybridized with a [(35)S]-labeled riboprobe complementary to B1R mRNA, stringently washed, and apposed to film and emulsion. The results of these studies revealed the presence of B1R mRNA throughout the rostral-caudal extent of the brain and spinal cord. In particular, labeled cells were seen in the cerebral and entorhinal cortex, dentate gyrus, and pyramidal neurons of the hippocampus, in the thalamus, hypothalamus, amygdala, pontine nuclei, spinal cord, and dorsal root ganglion. Together the present findings offer detailed information about the distribution of B1R mRNA in the primate brain and spinal cord and demonstrate a basal level of expression in the primate nervous system. Moreover, these data provide a foundation for understanding the central actions of kinins and their putative role in mediating a number of processes, including pain and nociception.
缓激肽1型和2型受体（B1R、B2R）是心血管稳态、炎症和痛觉感受的重要介质。虽然B2R在许多组织中组成性表达，但B1R的表达被认为不存在，而是在促炎条件下被诱导。然而，最近来自基因敲除小鼠的数据表明，B1R在中枢发挥作用以介导痛觉感受，这一发现提示B1R在脑和/或脊髓中组成性存在。本研究的目的是通过原位杂交评估B1R mRNA在非人类灵长类动物脑和脊髓中的定位，以进一步阐明B1R的生理作用。将来自猴脑和脊髓的恒冷箱切片与与B1R mRNA互补的[(35)S]标记核糖探针杂交，严格洗涤，然后与胶片和乳胶贴合。这些研究结果显示在脑和脊髓的头-尾全长范围内均存在B1R mRNA。特别地，在大脑皮质、内嗅皮质、齿状回、海马体的锥体细胞、丘脑、下丘脑、杏仁核、脑桥核、脊髓和背根神经节中可见标记细胞。本研究结果共同提供了关于B1R mRNA在灵长类动物脑和脊髓中分布的详细信息，并证明了其在灵长类神经系统中的基础表达水平。此外，这些数据为理解激肽的中枢作用及其在介导包括疼痛和痛觉感受在内的许多过程中的假定作用提供了基础。
