Phenylmethanesulfonyl fluoride, a serine protease inhibitor, suppresses naloxone-precipitated withdrawal jumping in morphine-dependent mice
Phenylmethanesulfonyl fluoride, a serine protease inhibitor, suppresses naloxone-precipitated withdrawal jumping in morphine-dependent mice
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DOI：
10.1016/j.npep.2012.11.002
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发表时间：
2013-06-01
期刊：
影响因子：
2.9
通讯作者：
Tan-No, Koichi
中科院分区：
文献类型：
--
作者：
Nemoto, Wataru;Sato, Tasuku;Tan-No, Koichi
我们以前已经表明，脑室内（i. c. v.）半胱氨酸蛋白酶抑制剂的给药抑制吗啡依赖小鼠中纳洛酮诱发的戒断跳跃，推测是通过抑制强啡肽降解（参见（Tan-No，K.，佐藤，T.，Shimoda，M.，中川斋岛Niijima，F.，川村，S.，Furuta，S.，佐藤，T.，Satoh，S.，Silberring，J.，特雷纽斯湖Tadano，T.，2010.半胱氨酸蛋白酶抑制剂对吗啡依赖小鼠纳洛酮催促戒断跳跃的抑制作用。神经肽44，279-283））。在本研究中，我们研究了丝氨酸蛋白酶抑制剂苯甲磺酰氟（PMSF）对吗啡依赖小鼠纳洛酮催促戒断跳跃的影响。每天两次皮下给予吗啡剂量（mg/kg/注射），持续2天[第1天（30）和第2天（60）]。在第3天，纳洛酮（8 mg/kg）腹腔内注射吗啡（60 mg/kg）后3 h，跳跃的数量立即记录20 min。纳洛酮引起的戒断跳跃显著抑制静脉注射PMSF（4 nmol），在诱导期每次吗啡治疗前5 min给药，在试验日不给药。组织纤溶酶原激活物（tPA），丝氨酸蛋白酶，纤溶酶原转化为纤溶酶，在前额皮质的表达显着增加吗啡依赖和戒断小鼠，与盐水治疗的小鼠相比。此外，反式-4-（氨甲基）-环己烷羧酸（300 pmol），一种抗纤溶酶剂，和（Tyr（1））-凝血酶受体激活肽7（0.45和2 nmol），一种蛋白酶激活受体-1（PAR-1）的拮抗剂，显着抑制纳洛酮诱发的戒断跳跃。本研究结果表明，PMSF抑制吗啡依赖小鼠纳洛酮催促戒断跳跃，大概是通过抑制属于丝氨酸蛋白酶家族的tPA和纤溶酶的活性，随后激活PAR-1。(c)2012爱思唯尔有限公司保留所有权利。
We have previously shown that intracerebroventricular (i.c.v.) administration of cysteine protease inhibitors suppresses naloxone-precipitated withdrawal jumping in morphine-dependent mice, presumably through the inhibition of dynorphin degradation (see (Tan-No, K., Sato, T., Shimoda, M., Nakagawasai, O., Niijima, F., Kawamura, S., Furuta, S., Sato, T., Satoh, S., Silberring, J., Terenius, L., Tadano, T., 2010. Suppressive effects by cysteine protease inhibitors on naloxone-precipitated withdrawal jumping in morphine-dependent mice. Neuropeptides 44, 279-283)). In the present study, we examined the effect of phenylmethanesulfonyl fluoride (PMSF), a serine protease inhibitor, on naloxone-precipitated withdrawal jumping in morphine-dependent mice. The doses of morphine (mg/kg per injection) were subcutaneously given twice daily for 2 days [day 1 (30) and day 2 (60)]. On day 3, naloxone (8 mg/kg) was intraperitoneally administered 3 h after the final injection of morphine (60 mg/kg), and the number of jumps was immediately recorded for 20 min. Naloxone-precipitated withdrawal jumping was significantly suppressed by i.c.v. administration of PMSF (4 nmol), given 5 min before each morphine treatment during the induction phase, with none given on the test day. The expression of tissue plasminogen activator (tPA), a serine protease that converts plasminogen to plasmin, in the prefrontal cortex was significantly increased in morphine-dependent and -withdrawal mice, as compared with saline-treated mice. Moreover, trans-4-(aminomethyl)-cyclohexanecarboxylic acid (300 pmol), an antiplasmin agent, and (Tyr(1))-thrombin receptor activating peptide 7 (0.45 and 2 nmol), an antagonist of protease activated receptor-1 (PAR-1), significantly suppressed naloxone-precipitated withdrawal jumping. The present results suggest that PMSF suppresses naloxone-precipitated withdrawal jumping in morphine-dependent mice, presumably through the inhibition of activities of tPA and plasmin belonging to the serine proteases family, which subsequently activates PAR-1. (c) 2012 Elsevier Ltd. All rights reserved.