Calcitonin Gene‐related Peptide Causes Intraspinal Spreading of Substance P Released by Peripheral Stimulation
Calcitonin Gene‐related Peptide Causes Intraspinal Spreading of Substance P Released by Peripheral Stimulation
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降钙素基因相关肽导致外周刺激释放的 P 物质在椎管内扩散
DOI：
10.1111/j.1460-9568.1992.tb00184.x
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发表时间：
1992
影响因子：
3.4
通讯作者：
A. Duggan
中科院分区：
文献类型：
--
作者：
H. Schaible;P. J. Hope;C. W. Lang;A. Duggan
实验采用巴比妥酸盐麻醉的脊椎猫，研究了降钙素基因相关肽（CGRP）对电神经刺激和有害机械刺激释放的免疫反应性物质P （ir - SP）在脊髓中的空间分布的影响。用带有C端导向SP抗体的微探针来评估ir - SP的存在。将CGRP微注射到2500、2000深度的微探针插入点附近的脊髓灰质中。使用微量（总计0.2-0.5 μl）含有浓度为10−5或10−3 m的CGRP的林格溶液（1500 μm和1000 μm），在未经治疗的脊髓电刺激胫骨神经（所有C纤维的阈值以上）引起集中在II层内和周围的ir - SP的释放。注射CGRP后，刺激相关的ir - SP在从脐带表面到腹角的区域被检测到。这种模式与显微注射合成肽酶抑制剂后观察到的相似（Duggan et al., Brain Res., 579, 261-269, 1992）。ir - SP进入位点的大规模扩张是时间依赖性的，在注射CGRP后10-40分钟内达到最大效果，在随后的探针中观察到逆转。当有害的机械刺激引起ir - SP释放时，微量注射CGRP后，也观察到ir - SP进入的区域出现类似的扩张。这些结果表明，CGRP在脊髓中的一个重要功能可能是控制释放的P物质进入的椎管内部位和神经元回路，可能是通过抑制负责肽降解的内多肽酶。
Experiments were performed in barbiturate‐anaesthetized, spinalized cats to investigate the effect of calcitonin gene‐related peptide (CGRP) on the spatial distribution of immunoreactive substance P (ir‐SP) in the spinal cord released by electrical nerve stimulation and noxious mechanical stimuli. The presence of ir‐SP was assessed with microprobes bearing C‐terminus‐directed antibodies to SP. CGRP was microinjected into the grey matter of the spinal cord near microprobe insertion sites at depths of 2500, 2000, 1500 and 1000 μm using minute amounts (in total 0.2–0.5 μl) of Ringer solution containing CGRP at a concentration of 10−5 or 10−3 M. In the untreated cord electrical stimulation of the tibial nerve (suprathreshold for all C fibres) elicited release of ir‐SP which was centred in and around the lamina II. After microinjection of CGRP, stimulation‐associated ir‐SP was detected in a region extending from the cord surface down to the ventral horn. This pattern was similar to that observed after the microinjection of synthetic peptidase inhibitors (Duggan et al., Brain Res., 579, 261–269, 1992). The large expansion of sites accessed by ir‐SP was time‐dependent, reaching a maximal effect within 10–40 min after microinjection of CGRP, and reversal was observed in subsequent probes. A similar expansion of the regions accessed by ir‐SP after microinjection of CGRP was also observed when release of ir‐SP was evoked by noxious mechanical stimulation of the toes. These results indicate that one important function of CGRP in the spinal cord may be the control of the intraspinal sites and neuronal circuits accessed by released substance P, possibly by inhibition of endopeptidases responsible for peptide degradation.