Inhibition of dynorphin-converting enzymes prolongs the antinociceptive effect of intrathecally administered dynorphin in the mouse formalin test.
Inhibition of dynorphin-converting enzymes prolongs the antinociceptive effect of intrathecally administered dynorphin in the mouse formalin test.
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在小鼠福尔马林试验中，强啡肽转化酶的抑制可延长鞘内注射强啡肽的抗伤害作用。
DOI：
10.1016/s0014-2999(96)00518-3
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发表时间：
1996
影响因子：
5
通讯作者：
K. Kisara
中科院分区：
文献类型：
--
作者：
K. Tan;A. Taira;T. Sakurada;M. Inoue;S. Sakurada;T. Tadano;T. Sato;C. Sakurada;I. Nylander;J. Silberring;L. Terenius;K. Kisara
多肽酶抑制剂对鞘内注射抗伤害性感觉的影响在小鼠福尔马林实验中检测强啡肽A和强啡肽B的作用。在接受I.T.治疗时在将0.5%福尔马林溶液注入大鼠后足背表面前5分钟，强啡肽A(0.5-2nmo1)和强啡肽B(2-8nmo1)可剂量依赖性地显著降低舔足反应。强啡肽A(2nmo1)和强啡肽B(8nmo1)分别在90min和60min内完全消失。半胱氨酸蛋白酶抑制剂对羟基汞苯甲酸酯和24.11酶内切酶抑制剂磷酰胺与强啡肽A或强啡肽B同时给予可显著延长两种强啡肽引起的抗伤害性感觉。然而，血管紧张素转换酶抑制剂卡托普利、通用氨基肽酶抑制剂Bestatin和丝氨酸蛋白酶抑制剂苯甲基磺酰氟则没有活性。强啡肽转换酶(S)将强啡肽相关多肽转化为脑啡肽和脑啡肽-精氨酸。[Leu5]脑啡肽或[Leu5]脑啡肽-Arg6，即使在高剂量(10nmol)时也不产生任何抗伤害作用。然而，[Leu5]脑啡肽-Arg6，而不是[Leu5]脑啡肽，在与磷酰胺联合给药时产生显著的抗伤害效应。因此，在磷酰胺存在的情况下，两种强啡肽引起的抗伤害性感觉的延长，可能是由于抑制了[Leu5]脑啡肽-Arg6的降解。本研究结果提示，强啡肽转换酶(S)可能是终止强啡肽A和强啡肽B在小鼠脊髓水平产生的抗伤害作用的重要酶(S)。
The effects of peptidase inhibitors on the antinociception induced by intrathecally (i.t.) administered dynorphin A and dynorphin B in the mouse formalin test were examined. When administered i.t. 5 min before the injection of 0.5% formalin solution into the dorsal surface of a hindpaw, dynorphin A (0.5–2 nmol) and dynorphin B (2–8 nmol) produced a dose-dependent and significant reduction of the paw-licking response. Dynorphin A (2 nmol) and dynorphin B (8 nmol)-induced antinociception disappeared completely within 90 min and 60 min, respectively. p-Hydroxymercuribenzoate, a cysteine proteinase inhibitor, and phosphoramidon, an endopeptidase 24.11 inhibitor simultaneously administered with dynorphin A or dynorphin B, significantly prolonged antinociception induced by both dynorphins. However, captopril, an angiotensin-converting enzyme inhibitor, bestatin (a general aminopeptidase inhibitor) and a serine proteinase inhibitor phenylmethanesulfonyl fluoride, were inactive. Dynorphin-converting enzyme(s) transform dynorphin-related peptides to [Leu5]enkephalin and [Leu5]enkephalin-Arg6. Neither [Leu5]enkephalin nor [Leu5]enkephalin-Arg6, even at high dose (10 nmol), produced any antinociceptive effect. However, [Leu5]enkephalin-Arg6, but not [Leu5]enkephalin, produced a significant antinociceptive effect when co-administered with phosphoramidon. Therefore, the prolongation of the antinociception induced by both dynorphins in the presence of phosphoramidon, may be due to the inhibition of [Leu5]enkephalin-Arg6degradation. The present results indicate that dynorphin-converting enzyme(s) may be important enzyme(s) responsible for terminating dynorphin-A- and dynorphin-B-induced antinociception at the spinal cord level in mice.
影响因子：
2.9
作者：
M. Pozsgay;C. Michaud;M. Liebman;M. Orłowski
通讯作者：
M. Pozsgay;C. Michaud;M. Liebman;M. Orłowski
膜结合垂体金属内肽酶：与脑啡肽酶明显相同。
DOI：
10.1016/0006-291x(81)91508-4
发表时间：
1981
影响因子：
3.1
作者：
Almenoff,J;Wilk,S;Orlowski,M
通讯作者：
Orlowski,M