Krysiak P S, Preiksaitis H G
Department of Physiology, University of Western Ontario, London, Ontario, Canada.
Gastroenterology. 2001 Jan;120(1):39-48. doi: 10.1053/gast.2001.20910.
BACKGROUND & AIMS: Tachykinins mediate nonadrenergic, noncholinergic excitation in the gastrointestinal tract, but their role in esophageal peristalsis remains unclear.
We used muscle strips from the distal third of human esophagus, obtained from patients undergoing esophagectomy for cancer, to investigate the contribution of tachykinins to nerve-mediated contractions. Isometric tension responses to agonists or electrical field stimulation were recorded in circular and longitudinal muscle strips.
Tachykinins produced concentration-dependent increases in tension in circular and longitudinal muscle strips, with the following order of potency: beta-Ala(8)-neurokinin (NK) A (4-10) > NKB > substance P, suggesting NK(2) receptor involvement. The NK(2) receptor antagonist, SR48968 (1 micromol/L), inhibited responses to tachykinins in both muscles. Nerve activation produced on- and off-contractions in circular muscle and a duration-contraction in longitudinal muscle. Atropine (10 micromol/L)-insensitive nerve-evoked contractions were identified for the 3 types of responses. SR48968 produced concentration-dependent inhibition of atropine-insensitive on- and off-contractions but had no effect on the duration-contraction. At low stimulus frequency (1 Hz), on-contractions showed greater sensitivity to SR48968 than off-contractions.
Nerve-mediated contractions in the human esophagus have a significant atropine-insensitive component. Tachykinins acting on NK(2) receptors can account for some, but not all, of this response, suggesting that other excitatory mechanisms also contribute.
速激肽介导胃肠道的非肾上腺素能、非胆碱能兴奋，但它们在食管蠕动中的作用仍不清楚。
我们使用了从因癌症接受食管切除术患者的食管远端三分之一处获取的肌肉条，来研究速激肽对神经介导收缩的作用。在环形和纵形肌肉条中记录对等激动剂或电场刺激的等长张力反应。
速激肽使环形和纵形肌肉条中的张力呈浓度依赖性增加，效力顺序如下：β-丙氨酸（8）-神经激肽（NK）A（4-10）>神经激肽B>P物质，提示涉及NK2受体。NK2受体拮抗剂SR48968（1微摩尔/升）抑制了两种肌肉对速激肽的反应。神经激活在环形肌肉中产生开-关收缩，在纵形肌肉中产生持续收缩。对于这3种反应，鉴定出阿托品（10微摩尔/升）不敏感的神经诱发收缩。SR48968对阿托品不敏感的开-关收缩产生浓度依赖性抑制，但对持续收缩无影响。在低刺激频率（1赫兹）下，开收缩对SR48968的敏感性高于关收缩。
人食管中神经介导的收缩有一个显著的阿托品不敏感成分。作用于NK2受体的速激肽可解释部分而非全部这种反应，提示其他兴奋机制也有作用。
