The Clayton Foundation Laboratories for Peptide Siology, The Salk Institute, La Jolla, CA 92037, USA.
Stress. 2001 Mar;4(1):13-24. doi: 10.3109/10253890109001140.
The present work investigated the effect of nitric oxide (NO) or carbon monoxide (CO) in the ACTH response to an immune signal [the intravenous injection of interleukin-1 β (IL-1β)] or to a neurogenic stressor (mild intermittent inescapable foot shocks). The arginine derivative N(ω)-L-arginine methylester (L-NAME), which non-specifically inhibits NO formation induced by all constitutive forms of NO synthase (NOS), significantly augmented the effect of IL-1P,but blockade of CO formation with metalloporphyrins was without effect. On the other hand, L-NAME blunted the effect of shocks on the early phase of ACTH release, while we had reported earlier that metalloporphyrins exerted a similar effect. This effect was mimicked by blockade of neuronal (n) NOS by N(ω)-Propyl-L-arginine (PA), although the resulting decrease in hormone levels was less than that induced by L-NAME. These results indicate that endogenous NO, but not CO, interferes with ACTH released by a peripheral immune signal. In contrast, NO formed by nNOS enhances the ability of shocks to induce ACTH secretion.
本研究旨在探讨一氧化氮（NO）或一氧化碳（CO）对促肾上腺皮质激素（ACTH）反应的影响，这种反应可由免疫信号（如静脉注射白细胞介素-1β（IL-1β））或神经应激源（如轻度间歇性不可逃避的足底电击）引起。精氨酸衍生物 N（ω）-L-精氨酸甲酯（L-NAME）可非特异性抑制所有组成型一氧化氮合酶（NOS）诱导的 NO 形成，它可显著增强 IL-1β的作用，但金属卟啉对 CO 形成的阻断作用则无影响。另一方面，L-NAME 减弱了电击对 ACTH 早期释放的影响，而我们之前曾报道过金属卟啉也有类似的作用。神经元（n）NOS 的阻断剂 N（ω）-丙基-L-精氨酸（PA）可模拟这种效应，尽管激素水平的下降幅度小于 L-NAME 引起的下降幅度。这些结果表明，内源性 NO 而非 CO 会干扰外周免疫信号引起的 ACTH 释放。相比之下，nNOS 形成的 NO 增强了电击诱导 ACTH 分泌的能力。
