Degradation of nociceptin (orphanin FQ) by mouse spinal cord synaptic membranes is triggered by endopeptidase-24.11: an in vitro and in vivo study.
Degradation of nociceptin (orphanin FQ) by mouse spinal cord synaptic membranes is triggered by endopeptidase-24.11: an in vitro and in vivo study.
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内肽酶 24.11 触发小鼠脊髓突触膜降解伤害感受肽（孤啡肽 FQ）：一项体外和体内研究。
DOI：
10.1016/s0006-2952(02)01295-9
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发表时间：
2002
影响因子：
5.8
通讯作者：
T. Sakurada
中科院分区：
文献类型：
--
作者：
C. Sakurada;S. Sakurada;Tohru Orito;K. Tan;T. Sakurada
我们在体内外实验中分析了痛敏素/痛敏素在FQ中与疼痛传递或调节相关的脊髓代谢途径。孤啡肽被脊髓突触膜降解。痛敏素的主要代谢产物为游离苯丙氨酸、痛敏素（1-13）和痛敏素（14-17）。伤害感受素的降解和主要裂解代谢产物伤害感受素（1-13）和伤害感受素（14-17）的积累均受到金属螯合剂以及内肽酶-24.11、thiorphan和phosphoramidon的特异性抑制剂的强烈抑制。此外，纯化的内肽酶-24.11水解伤害感受素的裂解位点（Lys 13-Leu 14键）相同的脊髓突触膜。最近，我们发现小剂量（fmol量级）鞘内注射痛敏肽可引起小鼠的抓、咬、舔等行为反应。在本研究中，我们研究了肽酶抑制剂对鞘内注射痛敏肽引起的小鼠行为反应的影响。Phosphoramidon同时注射与nociceptin相加增强nociceptin诱导的行为反应，而nociceptin诱导的行为反应不受bestatin，氨肽酶抑制剂或卡托普利，血管紧张素转换酶抑制剂。然而，通过联合注射phosphoramidon和bestatin增强了伤害感受素的作用，表明氨肽酶的抑制也可能有助于诱导对伤害感受素的行为反应。这些数据表明，内肽酶-24.11在小鼠脊髓水平的伤害感受素代谢的初始阶段起主要作用。
We analyzed spinal metabolic pathway of nociceptin/orphanin FQ related to pain-transmission or modulation in the both in vitro and in vivo experiments. Nociceptin was degraded by spinal synaptic membranes. Major metabolites of nociceptin were free phenylalanine, nociceptin (1–13) and nociceptin (14–17). Both the degradation of nociceptin and the accumulation of the major cleavage metabolites, nociceptin (1–13) and nociceptin (14–17), were strongly inhibited by a metal chelator and also by specific inhibitors of endopeptidase-24.11, thiorphan and phosphoramidon. Furthermore, purified endopeptidase-24.11 hydrolyzed nociceptin at the cleavage site (Lys13–Leu14bond) identical to that by spinal synaptic membranes. Recently, we have found that nociceptin, injected intrathecally at small doses (fmol order) elicits a behavioral response consisting of scratching, biting and licking in mice. In the present study, we have examined the effect of peptidase inhibitors on the behavioral response elicited by intrathecal injection of nociceptin in mice. Phosphoramidon simultaneously injected with nociceptin additively enhanced nociceptin-induced behavioral response, whereas the nociceptin-induced behavioral response was unaffected by either bestatin, an aminopeptidase inhibitor or captopril, an angiotensin-converting enzyme inhibitor. However, the nociceptin effect was potentiated by combined injection of phosphoramidon and bestatin, indicating that inhibition of aminopeptidase may also contribute to inducing the behavioral response to nociceptin. These data suggest that endopeptidase-24.11 plays a major role in initial stage of nociceptin metabolism at the spinal cord level in mice.
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DOI：
--
发表时间：
1997-08
期刊：
The Journal of pharmacology and experimental therapeutics
影响因子：
--
作者：
G. Rossi;L. Leventhal;E. Bolan;G. Pasternak
通讯作者：
G. Rossi;L. Leventhal;E. Bolan;G. Pasternak
小鼠外周孤啡肽 FQ/伤害感受肽镇痛。
影响因子：
6.1
作者：
Kolesnikov,YA;Pasternak,GW
通讯作者：
Pasternak,GW
DOI：
10.1006/bbrc.1996.5867
发表时间：
1997-01-13
影响因子：
3.1
作者：
Mathis, JP;RyanMoro, J;Pasternak, GW
通讯作者：
Pasternak, GW
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
孤啡肽 FQ/伤害感受素 (1-11) 的抗伤害感受类似物。
影响因子：
6.1
作者：
Mathis,JP;Goldberg,IE;Rossi,GC;Leventhal,L;Pasternak,GW
通讯作者：
Pasternak,GW