Great increase in antinociceptive potency of [Leu5]enkephalin after peptidase inhibition
Great increase in antinociceptive potency of [Leu5]enkephalin after peptidase inhibition
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DOI：
10.1254/jphs.fp0071318
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发表时间：
2008-02-01
影响因子：
3.5
通讯作者：
Oka, Tetsuo
中科院分区：
文献类型：
--
作者：
Akahori, Kazuhito;Kosaka, Kenya;Oka, Tetsuo
先前的体外研究表明，在与脑膜制剂孵育期间，[Leu（5）]脑啡肽的降解几乎完全被三种肽酶抑制剂的混合物所阻止：amastatin、captopril和phosphoramidon。目前的体内研究表明，[Leu（5）]脑啡肽对甩尾反应的抑制作用在第三脑室内给予三种肽酶抑制剂预处理后增加了500倍以上。在用两种肽酶抑制剂的任何组合预处理的大鼠中，[Leu（5）]脑啡肽产生的抗伤害效应显著小于用三种肽酶抑制剂预处理的大鼠，表明任何残留的单一肽酶都可以抑制显著量的[Leu（5）]脑啡肽。目前的数据，以及从以前的研究中获得的那些，清楚地表明，amastatin，captopril，和磷酰胺敏感的酶在短的内源性阿片肽，如五，七，和八肽，给药内第三脑室大鼠的失活中发挥重要作用。
Previous in vitro studies have shown that the degradation of [Leu(5)]enkephalin during incubation with cerebral membrane preparations is almost completely prevented by a mixture of three peptidase inhibitors: amastatin, captopril, and phosphoramidon. The present in vivo study shows that the inhibitory effect of [Leu(5)]enkephalin administered intra-third-ventricularly on the tail-flick response was increased more than 500-fold by the intra-third-ventricular pretreatment with the three peptidase inhibitors. The antinociceptive effect produced by the [Leu(5)]enkephalin in rats pretreated with any combination of two peptidase inhibitors was significantly smaller than that in rats pretreated with the three peptidase inhibitors, indicating that any residual single peptidase could inactivate significant amounts of the [Leu(5)]enkephalin. The present data, together with those obtained from previous studies, clearly demonstrate that amastatin-, captopril-, and phosphoramidon-sensitive enzymes play important roles in the inactivation of short endogenous opioid peptides, such as penta-, hepta-, and octa-peptides, administered intra-third-ventricularly to rats.