Matera M G, D'Agostino B, Costantino M, Amorena M, Lucarelli C, Rossi F
Institute of Pharmacology and Toxicology - Faculty of Medicine - 2nd University of Naples, Italy.
Life Sci. 1998;62(6):553-9. doi: 10.1016/s0024-3205(97)01152-1.
The aim of this study was to evaluate whether acetylcholine induces NO release. We determined the responses on the cholinergic component of the response to electrical field stimulation (EFS) the effects of L-nitro-arginine-methyl-ester (L-NAME; 1 mM), an inhibitor of NO synthase, of L-Arginine (L-ARG; 1 mM), a precursor of NO synthesis, and methoctramine (0.01-0.1-1 microM), an antagonist of M2 receptors, alone or associated with L-NAME. The experiments were performed on guinea pig isolated intact- or denuded-epithelium tracheal rings contracted in a frequency-dependent manner to EFS. At the maximum frequency tested (30 Hz), the contractile response elicited was 60.36 +/- 0.61% of acetylcholine (100 microM) contraction, while the maximal relaxant effect induced by EFS was -28.40 +/- 0.61% in epithelium intact preparations. A pretreatment with L-NAME significantly (P<0.05) increased the contraction (76.08 +/- 1.39%) and reduced the relaxation elicited by EFS. L-NAME effect on both EFS induced responses were statistically (P<0.05) reversed by the association L-NAME + L-ARG. Methoctramine (1 microM) enhanced contractile (P<0.05) (79.20 +/- 2.21%), as well as relaxant responses (-38.73 +/- 0.99%) elicited by EFS in guinea pig epithelium-intact tracheal rings; in a separate series of experiments, performed on guinea pig epithelium-intact rings, L-NAME increased the contractile responses to methoctramine (82.6 +/- 2.31), but reduced the relaxant ones (26.38 +/- 1.29). In contrast, at the maximum frequency tested, it increased only the contractile response, but not modify the relaxant one, in epithelium denuded rings. In conclusion, the present data showed that the release of acetylcholine from postganglionic cholinergic nerves plays an important role on NO formation and this effect may be modulate by epithelium.
本研究的目的是评估乙酰胆碱是否会诱导一氧化氮（NO）释放。我们测定了电场刺激（EFS）的胆碱能成分的反应，以及一氧化氮合酶抑制剂L-硝基-精氨酸甲酯（L-NAME；1 mM）、一氧化氮合成前体L-精氨酸（L-ARG；1 mM）和M2受体拮抗剂甲硫氧胺（0.01 - 0.1 - 1 microM）单独或与L-NAME联合使用时的效果。实验在豚鼠离体的完整或去上皮气管环上进行，这些气管环对EFS呈现频率依赖性收缩。在测试的最大频率（30 Hz）下，引发的收缩反应为乙酰胆碱（100 microM）收缩的60.36 +/- 0.61%，而在完整上皮制备物中，EFS诱导的最大舒张效应为 -28.40 +/- 0.61%。用L-NAME预处理显著（P<0.05）增加了收缩（76.08 +/- 1.39%）并减少了EFS引发的舒张。L-NAME对EFS诱导的两种反应的影响在统计学上（P<0.05）被L-NAME + L-ARG联合用药逆转。甲硫氧胺（1 microM）增强了豚鼠完整上皮气管环中EFS引发的收缩（P<0.05）（79.20 +/- 2.21%）以及舒张反应（-38.73 +/- 0.99%）；在另一系列对豚鼠完整上皮环进行的实验中，L-NAME增加了对甲硫氧胺的收缩反应（82.6 +/- 2.31），但减少了舒张反应（26.38 +/- 1.29）。相比之下，在测试的最大频率下，它仅增加了去上皮环中的收缩反应，而未改变舒张反应。总之，目前的数据表明，节后胆碱能神经释放的乙酰胆碱在NO形成中起重要作用，并且这种作用可能受上皮调节。
