Maggi C A, Patacchini R, Santicioli P, Giuliani S, Turini D, Barbanti G, Giachetti A, Meli A
Pharmacology Department, A. Menarini Pharmaceuticals, Florence, Italy.
Naunyn Schmiedebergs Arch Pharmacol. 1990 Mar;341(3):256-61. doi: 10.1007/BF00169740.
(1) Circularly-oriented muscle strips from the human ileum responded to electrical field stimulation (1-50 Hz) with frequency-related primary relaxation at low frequency and primary contractions at high frequencies of stimulation. Both responses were abolished or markedly reduced by tetrodotoxin (1 microM). (2) Atropine (3 microM) or omega conotoxin (0.1 microM) reduced but dit not abolish contraction to electrical field stimulation and enhanced the relaxation. Omega conotoxin (0.1 microM) did not affect carbachol-induced contraction nor isoprenaline-induced relaxation. (3) Neurokinin A and substance P (1 nM-1 microM) produced a concentration-dependent contraction. The NK-1 receptor selective agonist, [Pro9]SP sulfone and the NK-2 receptor selective agonist [beta Ala8]NKA(4-10) produced a contraction superimposable to that of substance P and neurokinin A, respectively. On the other hand, [MePhe7]-neurokinin B, an NK-3 receptor selective agonist was ineffective up to 1 microM. The response to substance P or neurokinin A was unaffected by atropine (3 microM). (4) Galanin, up to 0.1 microM, produced a weak and inconsistent contraction. (5) Vasoactive intestinal polypeptide (10 nM-1 microM) produced a concentration-dependent relaxation while human alpha calcitonin gene-related peptide exerted a weak and inconsistent relaxant effect. (6) These findings indicate that both cholinergic excitatory and non-cholinergic inhibitory nerves affect the motility of the circular muscle of the human small intestine. Transmitter release from excitatory nerves seems largely mediated by activation of omega conotoxin-sensitive (N-type) calcium channels. Tachykinins exert a potent contractile effect, independently of cholinergic nerves, via NK-1 and NK-2 receptors.
(1) 取自人回肠的环形肌条对电场刺激（1 - 50 Hz）产生反应，在低频时出现与频率相关的原发性舒张，在高频刺激时出现原发性收缩。两种反应均被河豚毒素（1 microM）消除或显著减弱。(2) 阿托品（3 microM）或ω芋螺毒素（0.1 microM）可减弱但未消除对电场刺激的收缩反应，并增强舒张反应。ω芋螺毒素（0.1 microM）不影响卡巴胆碱诱导的收缩或异丙肾上腺素诱导的舒张。(3) 神经激肽A和P物质（1 nM - 1 microM）产生浓度依赖性收缩。NK - 1受体选择性激动剂[Pro9]SP砜和NK - 2受体选择性激动剂[βAla8]NKA(4 - 10)分别产生与P物质和神经激肽A叠加的收缩。另一方面，NK - 3受体选择性激动剂[MePhe7] - 神经激肽B在高达1 microM时无效。对P物质或神经激肽A的反应不受阿托品（3 microM）影响。(4) 甘丙肽在高达0.1 microM时产生微弱且不一致的收缩。(5) 血管活性肠肽（10 nM - 1 microM）产生浓度依赖性舒张，而人α降钙素基因相关肽发挥微弱且不一致的松驰作用。(6) 这些发现表明，胆碱能兴奋性神经和非胆碱能抑制性神经均影响人小肠环形肌的运动性。兴奋性神经递质的释放似乎主要由ω芋螺毒素敏感的（N型）钙通道激活介导。速激肽通过NK - 1和NK - 2受体发挥强大的收缩作用，与胆碱能神经无关。
