Major metabolites of substance P degraded by spinal synaptic membranes antagonize the behavioral response to substance P in rats.
Major metabolites of substance P degraded by spinal synaptic membranes antagonize the behavioral response to substance P in rats.
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脊髓突触膜降解的 P 物质的主要代谢物会拮抗大鼠对 P 物质的行为反应。
DOI：
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发表时间：
1999
期刊：
影响因子：
--
通讯作者：
T. Sakurada
中科院分区：
文献类型：
--
作者：
C. Sakurada;C. Watanabe;S. Sakurada;K. Tan;T. Sakurada
P物质（SP）被大鼠脊髓突触膜降解。裂解产物通过反相高效液相色谱法分离，并通过氨基酸组成分析鉴定。主要产物为苯丙氨酸、SP（1-4）、SP（1-6）、SP（1-7）、SP（10-11）和SP（8-9）。SP的降解和积累的主要裂解产物强烈抑制金属螯合剂，邻菲咯啉，也由特定的抑制剂内肽酶-24.11，thiorphan，和phosphoramidon。因此，内肽酶-24.11在大鼠脊髓中的SP降解中起主要作用。用脊髓突触膜孵育后检测到的N-末端片段SP（1-7）和SP（1-4）在体内检测对鞘内（IT）注射SP（3.0 nmol）诱导的大鼠抓、咬和舔反应的拮抗作用。当IT与SP合用时，SP（1-7）和SP（1-4）对SP的行为反应有明显的抑制作用，ED_（50）分别为135.0pmol和6.2nmol。这些结果表明，脊髓中SP的降解不仅导致母体肽的失活，而且还可能导致N末端SP片段的形成，这些片段显示出新的生理功能。
Substance P (SP) was degraded by synaptic membranes of rat spinal cord. Cleavage products were separated by reversed phase high performance liquid chromatography and identified by amino acid composition analyses. Major products of SP were phenylalanine, SP(1-4), SP(1-6), SP(1-7), SP(10-11), and SP(8-9). Both the degradation of SP and the accumulation of the major cleavage products were strongly inhibited by a metal chelator, o-phenanthroline, and also by specific inhibitors of endopeptidase-24.11, thiorphan, and phosphoramidon. Thus, endopeptidase-24.11 plays a major role in SP degradation in the rat spinal cord. N-Terminal fragments, SP(1-7) and SP(1-4), detected after incubation with spinal synaptic membranes were examined in vivo for antagonism against the scratching, biting, and licking response induced by intrathecal (IT) injection of SP (3.0 nmol) in rats. When IT coadministered with SP, SP(1-7) and SP(1-4) produced a significant inhibition of behavioral response to SP with ED50 of 135.0 pmol and 6.2 nmol, respectively. These results suggest that the degradation of SP in the spinal cord is not only responsible for inactivation of parent peptide, but may also lead to the formation of N-terminal SP-fragments which are shown to display a novel physiological function.
鉴定介导 P 物质诱导的小鼠行为的新型受体。
影响因子：
5
作者：
Mousseau,DD;Sun,X;Larson,AA
通讯作者：
Larson,AA
血管紧张素转换酶的大鼠脑同工酶。
DOI：
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发表时间：
1985
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Strittmatter,SM;Thiele,EA;Kapiloff,MS;Snyder,SH
通讯作者：
Snyder,SH