Jeftinija S, Liu F, Jeftinija K, Urban L
Department of Veterinary Anatomy, Iowa State University, Ames 50011.
Regul Pept. 1992 Jun 11;39(2-3):123-35. doi: 10.1016/0167-0115(92)90534-2.
The neurotoxic effect of capsaicin has been shown to be selective on a subpopulation of small dorsal root ganglion neurons in newborn animals. The aim of this study was to provide evidence of the long lasting effect of capsaicin and its ultrapotent analog resiniferatoxin (RTX) on sensory peptidergic neurons maintained in organotypic cultures. The effects of the two irritants were examined on neurons that contained substance P (SP) and calcitonin gene-related peptide (CGRP). Exposure of the cultures to 10 microM capsaicin and 100 nM RTX for periods of 2 days or longer resulted in almost complete elimination of SP-immunoreactive (IR) neurites and reduction, but not elimination, of CGRP-IR neurites. In addition, both 10 microM capsaicin and 100 nM RTX significantly reduced the number of SP- and CGRP-IR cell bodies within DRG explants. Capsaicin in 100 microM concentration produced complete elimination of SP-IR fibers and a greater decrease in the number of CGRP-IR fibers, but failed to completely eliminate IR cell bodies. Exposure of the cultures to the irritants in the same concentrations for 90 min did not produce a measurable effect on SP- or CGRP-IR in neurites or cell bodies. It is important to establish that the effect of capsaicin and RTX on cultured neurons was of long duration (longer than 4 days) and is therefore different from depletion of peptides. These findings demonstrate that processes of cultured sensory neurons are much more sensitive to capsaicin and RTX than cell bodies. Furthermore, our results show that SP-IR neuronal elements are more sensitive to capsaicin than CGRP-IR elements. These data suggest that cultured sensory neurons express the functional properties of differentiated sensory neurons in vivo.
辣椒素的神经毒性作用已被证明对新生动物的一小部分背根神经节小神经元具有选择性。本研究的目的是提供证据，证明辣椒素及其超效类似物树脂毒素（RTX）对维持在器官型培养物中的感觉肽能神经元具有长期影响。研究了这两种刺激物对含有P物质（SP）和降钙素基因相关肽（CGRP）的神经元的影响。将培养物暴露于10微摩尔/升的辣椒素和100纳摩尔/升的RTX中2天或更长时间，几乎完全消除了SP免疫反应性（IR）神经突，并减少了CGRP-IR神经突，但并未消除。此外，10微摩尔/升的辣椒素和100纳摩尔/升的RTX均显著减少了背根神经节外植体中SP-和CGRP-IR细胞体的数量。100微摩尔/升浓度的辣椒素完全消除了SP-IR纤维，CGRP-IR纤维数量减少得更多，但未能完全消除IR细胞体。将培养物暴露于相同浓度的刺激物中90分钟，对神经突或细胞体中的SP-或CGRP-IR没有产生可测量的影响。重要的是要确定辣椒素和RTX对培养神经元的作用持续时间较长（超过4天），因此与肽的消耗不同。这些发现表明，培养的感觉神经元的神经突比细胞体对辣椒素和RTX更敏感。此外，我们的结果表明，SP-IR神经元成分比CGRP-IR成分对辣椒素更敏感。这些数据表明，培养的感觉神经元在体内表达了分化的感觉神经元的功能特性。
