Pain relief substance in spinal cord

脊髓中的止痛物质

• 批准号: 02671060
• 负责人: HAZATO Tadahiko
• 金额: $ 1.47万
• 依托单位: Tokyo Metropolitan Institute of Medical Science.
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1990
• 资助国家: 日本
• 起止时间: 1990 至 1992
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-02671060/
• 关键词: Spinorphin; Spinal cord; Hemorphin; Enkephalin degrading enzyme inhibitor; 分解酵素阻害物質; Enkephalin分解酵素阻害物質

We isolated a potent inhibitor for enkephalin degrading enzymes from the bovine spinal cord, and determined its amino-acid sequence and pharmacological action. This new substance is composed of heptapeptide (Leu-Val-Val-Tyr-Pro-Trp-Thr), and has been named by us 'Sinorphin". This present study is to deterain the opioid activity and the existance of Spinorphin degrading enzyme in human spinal cord. The intracisternally injected Spinorphin produced analgesic effects in a dose -dependent manner, in dose of 100-200nnol/mouse. The analgesic effect reached the maximum within 5min and dissapeared afterl5-6Onin. Spinorphin also produces a dose-related inhibition of electrically evoked contractions of the mouse vas deferens and the guinea pig ileum. These inhibitory effects could be completely antagonised bynaloxone. The diiscovery in the bovine spinal cord of endogenoue heptapeptide, Spinorphin with potent opioid activity raises a number of pertinent questions which cannot be adequately dealt with in this study. It will now be possible, however, to test the very hypothesis that this petides act as neurotransmitters or neuromodulations at synaptic junction.

我们从牛脊髓中分离出一种脑啡肽降解酶的有效抑制剂，并测定了其氨基酸序列和药理作用。这种新物质是由七肽(Leu-Val-Val-Tyr-Pro-Trp-Thr)组成的，我们将其命名为辛诺芬。本研究旨在检测人脊髓中阿片类物质的活性及是否存在Spinnoin降解酶。脑池内注射Spinnoin对小鼠的镇痛作用呈剂量依赖性，剂量为100-200nnol/只。镇痛作用在5分钟内达到最大值，15-6分钟后消失。多诺芬还对小鼠输精管和豚鼠回肠的电诱发收缩产生剂量相关的抑制作用。这些抑制作用可被苯那洛酮完全拮抗。在牛脊髓中发现内源性七肽、旋诺芬具有强大的阿片类药物活性，这提出了一些在本研究中无法充分解决的相关问题。然而，现在有可能检验这样一个假设，即这些小肽在突触连接处起到神经递质或神经调制的作用。

项目成果

羽里 忠彦: "ウシ脊髄中のlnkephalin分解酵素阻害物質" 第63回日本生化学会大会. 62. 575 (1990)

Tadahiko Hanari：“牛脊髓中的脑啡肽降解酶抑制剂”第 63 届日本生化学会年会 62. 575 (1990)。

Nishimura, K: "Endogenous inhibitor of enkephalin degrading enzyme" JPN J Anesthesiology. 39. S284 (1990)

Nishimura, K：“脑啡肽降解酶的内源性抑制剂”JPN J 麻醉学。

Hasumi, K: "A study of leucine enkephalin-like substance and enkephalin degrading enzyme activity in human cerebrospinal fluid." JPN Anaesthesia. J. review. 4. 321-323 (1991)

Hasumi, K：“人类脑脊液中亮氨酸脑啡肽样物质和脑啡肽降解酶活性的研究。”

西村 欣也: "Enkephalin分解酔素に対する内因性阻害物質の研究" 日本臨床薬理麻酔. 4. 127 (1991)

Kinya Nishimura：“脑啡肽降解麻醉剂的内源性抑制剂的研究”日本临床药理学麻醉。 4. 127 (1991)

Nishimura, K: "Study of endogenous inhibitor of enkephalin degrading enzyme" JSPA Pharmacoanesthesilogy. 4. 127 (1991)

Nishimura, K：“脑啡肽降解酶内源性抑制剂的研究”JSPA 药物麻醉学。