l -精氨酸/一氧化氮神经通路参与牛食管沟非肾上腺素能、非胆碱能松弛

M. V. Barahona, S. Sánchez-Fortún, M. D. San Andrés, E. Ballesteros, J. Contreras, M. San Andrés
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引用次数: 9

摘要

采用免疫组织化学和组织化学染色技术研究了牛食管沟一氧化氮合酶(NOS)免疫反应性和烟酰胺腺嘌呤二核苷酸磷酸二磷酸酶(NADPH-d)活性的分布和定位。体外功能研究NOS-免疫反应性(IR)和NADPH-d染色与牛食管沟活动中涉及l -精氨酸/一氧化氮神经通路的平滑肌松弛的相关性。NOS-IR和NADPH-d表达于肌肠、粘膜下和肌内神经节的神经细胞体以及分布在血管周围和牛食管沟不同肌肉层的神经纤维中。用胍乙啶(10−5 M)和阿托品(10−7 M)分别阻断去甲肾上腺素能神经传递和毒碱受体,在食管沟条中,电场刺激(EFS, 0.5-32 Hz, 1 ms持续时间,20 s序列)诱导松弛,实际上被河河鱼毒素(TTX, 10−6 M)所消除。显著抑制EFS引起的松弛。这种抑制作用被l -精氨酸(L-arg, 5 × 10−3 M)部分逆转,而D-NOARG (3 × 10−5 M)对efs诱导的弛缓没有影响。作为NaNO2(10−6-10−3 M)和s -亚硝基- l -半胱氨酸(10−7-10−4 M)酸化溶液添加的NO引起牛食管沟的浓度依赖性松弛。L-arg (3 × 10−5 M)对牛食管沟的神经传导无影响。神经和神经节中NO合成酶的存在,以及NO介导的平滑肌松弛的药理学证据表明,L-arg/NO神经元通路参与了牛食管沟的抑制性神经传递。
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Involvement of the L-arginine/nitric oxide neural pathway in non-adrenergic, non-cholinergic relaxation of the bovine oesophageal groove
1. The distribution and localization of nitric oxide synthase (NOS) immunoreactivity and nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) activity in the bovine oesophageal groove were investigated by immnunohistochemical and histochemical staining techniques. Functional in vitro studies were performed to correlate the presence of NOS-immunoreactivity (IR) and NADPH-d staining with smooth muscle relaxations involving the L-arginine/nitric oxide neural pathway in the bovine oesophageal groove activity. 2. NOS-IR and NADPH-d were expressed in nerve cell bodies of the myenteric, submucosal and intramuscular ganglia, and in nerve fibres distributed around blood vessels and throughout the different muscular layers of the bovine oesophageal groove. 3. In oesophageal groove strips treated with guanethidine (10(-5) M) and atropine (10(-7) M) to block noradrenergic neurotransmission and muscarinic receptors, respectively, electrical field stimulation (EFS, 0.5-32 Hz, 1 ms duration, 20-s trains) induced relaxations which were practically abolished by tetrodotoxin (TTX, 10(-6) M). 4. Incubation with an inhibitor of nitric oxide synthesis, NG-nitro-L-arginine (L-NOARG, 3 x 10(-5) M), significantly inhibited relaxations induced by EFS. This inhibition was partially reversed by L-arginine (L-arg, 5 x 10(-3) M). D-NOARG (3 x 10(-5) M) had no effect on EFS-induced relaxations. 5. NO added as an acidified solution of NaNO2 (10(-6) - 10(-3) M) and S-nitroso-L-cysteine (10(-7) - 10(-4) M) caused concentration-dependent relaxations of the bovine oesophageal groove. These relaxations were unaffected by L-NOARG (3 x 10(-5) M). 6. The presence of NO-synthesizing enzyme in nerves and ganglia, and the pharmacological evidence for NO-mediated smooth muscle relaxation suggested that the L-arg/NO neuronal pathway is involved in the inhibitory neurotransmission of the bovine oesophageal groove.
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Issue Information Autonomic and Autacoid Pharmacology: Goodbye and thank you Attenuation of the anti-contractile effect of cooling in the rat aorta by perivascular adipose tissue Retraction: Dopamine receptor immunohistochemistry in the rat choroid plexus. Issue Information
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