INVOLVEMENT OF NITRIC-OXIDE IN INTRACEREBROVENTRICULAR BETA-ENDORPHIN-INDUCED NEURONAL RELEASE OF METHIONINE-ENKEPHALIN
INVOLVEMENT OF NITRIC-OXIDE IN INTRACEREBROVENTRICULAR BETA-ENDORPHIN-INDUCED NEURONAL RELEASE OF METHIONINE-ENKEPHALIN
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DOI：
10.1016/0006-8993(95)00065-x
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发表时间：
1995-03-27
期刊：
影响因子：
2.9
通讯作者：
QUOCK, RM
中科院分区：
文献类型：
--
作者：
HARA, S;KUHNS, ER;QUOCK, RM
先前的工作表明，大鼠中一氧化二氮（N2 O）的抗伤害性效应至少部分是由β-内啡肽（β-EP）介导的，并且中枢给予β-EP刺激大鼠脊髓中甲硫氨酸-脑啡肽（ME）的释放。由于已发现抑制中枢一氧化氮（NO）的产生会抑制N2 O的抗伤害性感受，因此我们研究了NO可能参与i. c. v. β-EP释放脊髓ME。将乌拉坦麻醉的雄性Sprague-Dawley大鼠鞘内（i. t.）用人工脑脊液（aCSF）灌注，并测定灌注液组分的免疫反应性（i.r.）ME。i.t.通过用含有100 μ M L-N-G-硝基精氨酸（L-NOARG）（一种NO合酶（NOS）的抑制剂）的aCSF灌注动物，灌注液被显著抑制。进一步向aCSF中加入50 μ M L-精氨酸（L-ARG），而不是D-精氨酸（D-ARG），逆转了L-NOARG对ME变化的抑制。然而，L-ARG的效力随着L-ARG浓度的增加而降低。另一方面，增加浓度的L-NOARG在aCSF中的250 μ M未能产生更大的抑制β-EP-诱导的ME增加。这些研究结果表明，NO可能介导β-EP-诱导的释放ME在脊髓和干扰这种机制可能是一种解释的拮抗作用的N2 O抗大鼠伤害性NOS抑制剂。
Previous work has suggested that the antinociceptive effect of nitrous oxide (N2O) in rats is mediated, at least in part, by beta-endorphin (beta-EP) and that centrally administered beta-EP stimulates release of methionine-enkephalin (ME) in the rat spinal cord. Since inhibition of central nitric oxide (NO) production has been found to suppress N2O antinociception, we examined the possible involvement of NO in the release of spinal cord ME by i.c.v. beta-EP. Urethane-anesthetized, male Sprague-Dawley rats were intrathecally (i.t.) perfused with artificial cerebrospinal fluid (aCSF) and fractions of perfusate were assayed for immunoreactive (i.r.) ME. The beta-EP-induced increase in ME concentration in the i.t. perfusate was significantly suppressed by perfusing the animal with aCSF containing 100 mu M L-N-G-nitro arginine (L-NOARG), an inhibitor of NO synthase (NOS). The further addition of 50 mu M L-arginine (L-ARG), but not D-arginine (D-ARG), to the aCSF reversed the suppression of the ME change by L-NOARG. However, the potency of L-ARG decreased with increasing concentrations of L-ARG. On the other hand, increasing the concentration of L-NOARG in the aCSF to 250 mu M failed to produce a greater suppression of the beta-EP-induced increase in ME. These findings suggest that NO may mediate the beta-EP-induced release of ME in the spinal cord and that interference with this mechanism might be an explanation for the antagonism of N2O antinociception in rats by NOS inhibitors.