一氧化氮，一种肠道非肾上腺素能-非胆碱能舒张性递质：使用磷酸二酯酶V和一氧化氮合酶抑制的证据

Nitric oxide, an enteric nonadrenergic-noncholinergic relaxant transmitter: evidence using phosphodiesterase V and nitric oxide synthase inhibition.

作者信息

Williams S J, Parsons M E

机构信息

Biosciences Division, University of Hertfordshire, Hatfield.

出版信息

Br J Pharmacol. 1995 Sep;116(2):1789-96. doi: 10.1111/j.1476-5381.1995.tb16664.x.

DOI:10.1111/j.1476-5381.1995.tb16664.x

PMID:8528561

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1909085/

Abstract

The effects of NG-nitro-L-arginine (L-NOARG), a nitric oxide synthase inhibitor, and SK&F 96231, a phosphodiesterase type V inhibitor, on electrical field stimulated (EFS) nonadrenergic noncholinergic (NANC) relaxations of rat fundal strips, guinea-pig isolated ileum longitudinal muscle with intact myenteric plexus, and guinea-pig taenia caeci were investigated. 2. Reproducible repeated control random EFS frequency-response curves were obtained for all three tissues. 3. Depending on the frequency of stimulation, L-NOARG (10(-4)-5 x 10(-3) M) caused either a complete or partial inhibition of the NANC-induced relaxations of the rat fundal strips and the guinea-pig isolated ileum longitudinal muscle with intact myenteric plexus, but not of the guinea-pig taenia caeci. The inhibitory action of L-NOARG was partially or totally reversed, depending on the tissue, by L-arginine (5 x 10(-3) M). 4. SK&F 96231 (10(-6)-10(-4) M) caused a concentration- and frequency-dependent potentiation of both the size and duration of the EFS-induced NANC relaxant response of rat fundal strips and guinea-pig isolated ileum longitudinal muscle with intact myenteric plexus, but not of the guinea-pig taenia caeci. 5. Zaprinast, another phosphodiesterase type V inhibitor (10(-6)-10(-4) M) caused a concentration- and frequency-dependent potentiation of the NANC relaxant responses to EFS of rat fundal strips. 6. SK&F 96231 and zaprinast alone (10(-6)-10(-4) M) caused a concentration-dependent relaxation of the agonist-induced tone of all three tissues with the maximum degree of relaxation found to be in the order stomach < ileum < caecum. This is the reverse order for ability of SK&F 96231 to potentiate relaxant responses to EFS. 7. These results suggest NO is involved in the NANC nerve-mediated relaxation of rat fundal strips and guinea-pig isolated ileum longitudinal muscle with intact myenteric plexus, but not the guinea-pig taenia caeci.

摘要

研究了一氧化氮合酶抑制剂NG-硝基-L-精氨酸（L-NOARG）和磷酸二酯酶V型抑制剂SK&F 96231对电场刺激（EFS）大鼠胃底条、具有完整肠肌丛的豚鼠离体回肠纵行肌以及豚鼠盲肠带的非肾上腺素能非胆碱能（NANC）舒张的影响。2. 获得了所有三种组织可重复的对照随机EFS频率-反应曲线。3. 根据刺激频率，L-NOARG（10⁻⁴ - 5×10⁻³ M）对大鼠胃底条和具有完整肠肌丛的豚鼠离体回肠纵行肌的NANC诱导舒张产生完全或部分抑制，但对豚鼠盲肠带无此作用。L-精氨酸（5×10⁻³ M）可部分或完全逆转L-NOARG的抑制作用，具体取决于组织。4. SK&F �6231（10⁻⁶ - 10⁻⁴ M）对大鼠胃底条和具有完整肠肌丛的豚鼠离体回肠纵行肌的EFS诱导的NANC舒张反应的大小和持续时间产生浓度和频率依赖性增强，但对豚鼠盲肠带无此作用。5. 另一种磷酸二酯酶V型抑制剂扎普司特（10⁻⁶ - 10⁻⁴ M）对大鼠胃底条的EFS的NANC舒张反应产生浓度和频率依赖性增强。6. SK&F 96231和扎普司特单独使用（10⁻⁶ - 10⁻⁴ M）对所有三种组织的激动剂诱导张力产生浓度依赖性舒张，最大舒张程度顺序为胃＜回肠＜盲肠。这与SK&F 96231增强对EFS舒张反应的能力顺序相反。7. 这些结果表明，一氧化氮参与了大鼠胃底条和具有完整肠肌丛的豚鼠离体回肠纵行肌的NANC神经介导舒张，但不参与豚鼠盲肠带的该过程。