Role of nitric oxide in interleukin 2-induced corticotropin-releasing factor release from incubated hypothalami.
Role of nitric oxide in interleukin 2-induced corticotropin-releasing factor release from incubated hypothalami.
复制标题
一氧化氮在白细胞介素 2 诱导的下丘脑释放促肾上腺皮质激素释放因子中的作用。
DOI：
10.1073/pnas.90.8.3383
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发表时间：
1993
影响因子：
11.1
通讯作者：
McCann,SM
中科院分区：
文献类型：
--
作者：
Karanth,S;Lyson,K;McCann,SM
最近证明白细胞介素 2 (IL-2) 可刺激下丘脑释放促肾上腺皮质激素释放因子 (CRF)。细胞因子诱导一氧化氮合酶 (NOS)，一种将 L-精氨酸转化为 L-瓜氨酸和一氧化氮 (NO) 的酶。 NO被认为是这些药物的细胞毒性作用的原因。 NOS 的组成形式存在于中枢神经系统的神经元中，NO 似乎在小脑和海马功能中发挥神经递质作用。我们探讨了 IL-2 和突触递质可能通过 NO 释放 CRF 的可能性。使用在 Krebs-Ringer 碳酸氢盐缓冲液中体外培养的中基底下丘脑 (MBH)，研究了 NOS 底物 L-精氨酸和 NOS 竞争性抑制剂 NG-单甲基-L-精氨酸 (NMMA) 对 IL-2 诱导的 CRF 释放的影响。孵育 30 分钟后，L-精氨酸不会改变基础和 IL-2 诱导的 CRF 释放，但当 MBH 孵育 30 分钟以上时，会显着提高基础和 IL-2 诱导的 CRF 释放，可能是因为在最初的 30 分钟孵育期后内源底物已耗尽。在 30 分钟的孵育中，卡巴胆碱（一种乙酰胆碱模拟药物）和去甲肾上腺素都会刺激 CRF 的释放。在存在卡巴胆碱(10(-7)M)和IL-2(10(-13)M)的情况下，MBH的孵育具有累加效应。另一方面，MBHs与去甲肾上腺素(10(-6)M)和IL-2(10(-13)M)共孵育没有产生任何相加效应。添加1或3 x 10(-4) M NOS抑制剂NMMA完全抑制IL-2诱导的CRF释放以及IL-2加卡巴胆碱引起的CRF释放。相反，去甲肾上腺素诱导的CRF释放不被3 x 10(-4) M NMMA阻断。数据表明IL-2可以激活组成型NOS，导致NO释放增加，从而激活CRF释放。 NO 似乎也参与由卡巴胆碱诱导的 CRF 释放，但不参与由去甲肾上腺素诱导的 CRF 释放。
Stimulation of corticotropin-releasing factor (CRF) release from the hypothalamus by interleukin 2 (IL-2) was recently demonstrated. Cytokines induce nitric oxide synthase (NOS), an enzyme that converts L-arginine into L-citrulline and nitric oxide (NO). NO is believed to be responsible for the cytotoxic action of these agents. The constitutive form of NOS occurs in neurons in the central nervous system and NO appears to play a neurotransmitter role in cerebellar and hippocampal function. We explored the probability that IL-2 and synaptic transmitters might release CRF via NO. The effects of L-arginine, the substrate for NOS, and NG-monomethyl-L-arginine (NMMA), a competitive inhibitor of NOS, on IL-2-induced CRF release were studied using mediobasal hypothalami (MBHs) incubated in vitro in Krebs-Ringer bicarbonate buffer. L-Arginine did not alter basal and IL-2-induced CRF release after 30 min of incubation but significantly elevated both basal and IL-2-induced CRF release when MBHs were incubated 30 min longer, presumably because the endogenous substrate had been depleted after the initial 30-min incubation period. In 30-min incubations, both carbachol, an acetylcholineomimetic drug, and norepinephrine stimulated CRF release. There was an additive effect of incubation of the MBHs in the presence of carbachol (10(-7) M) and IL-2 (10(-13) M). On the other hand, coincubation of MBHs with norepinephrine (10(-6) M) and IL-2 (10(-13) M) did not produce any additive effect. Addition of NMMA, an inhibitor of NOS, at 1 or 3 x 10(-4) M completely suppressed IL-2-induced release of CRF as well as that caused by IL-2 plus carbachol. In contrast, the release of CRF induced by norepinephrine was not blocked by 3 x 10(-4) M NMMA. The data indicate that IL-2 can activate constitutive NOS leading to increased NO release, which activates CRF release. It appears that NO is also involved in the release of CRF induced by carbachol but not by norepinephrine.