Reynolds J C, Dukehart M R, Ouyang A, Cohen S
J Clin Invest. 1986 Feb;77(2):436-40. doi: 10.1172/JCI112322.
The purpose of this study was to determine the interactions between bombesin and substance P at the feline lower esophageal sphincter (LES). Intraluminal pressures were recorded using a fixed, perfused catheter assembly. Myoelectrical activity was recorded using bipolar Ag-AgCl serosal electrodes. Bombesin, i.v., gave a dose-dependent increase in LES pressure and electronically counted spike activity. The threshold dose was 10(-7) g/kg, while the maximal dose, 10(-5) g/kg, increased LES pressure by 65.5 +/- 14.8 mmHg. The neuroantagonist, tetrodotoxin, decreased the LES response to bombesin by 74.1% +/- 7.9% (P less than 0.05), but had no significant effect on the LES response to substance P. The sphincteric response to bombesin was not inhibited by bilateral cervical vagotomy, atropine, propranolol, or phentolamine (P less than 0.10). Bombesin tachyphylaxis abolished the LES response to bombesin but had no effect on the response to substance P. Conversely, substance P tachyphylaxis completely abolished the LES response to bombesin (P less than 0.001). The substance P antagonist [D-Pro2, D-Trp7,9]substance P also significantly inhibited the LES response to bombesin (P less than 0.05). Acidification of the distal esophagus with 2.0 ml of 0.1 N HCl increased LES pressure by 32.5 +/- 5.2 mmHg (P less than 0.02). The LES response to acid was inhibited by bombesin tachyphylaxis (maximal pressure response, 4.7 +/- 2.1 mmHg, P less than 0.01 compared with control acid response). The tachyphylaxis techniques were specific for the peptides giving no effect on the LES responses to phenylephrine, bethanechol, or pentagastrin. We drew the following conclusions: (a) bombesin increased feline LES pressure via nonvagal neural pathways that were insensitive to adrenergic or cholinergic antagonists; (b) bombesin may be involved in the enteric pathways that mediate the feline LES response to distal esophageal acidification; and (c) substance P mediates the effect of bombesin at the LES and is a neurotransmitter in the LES response to acidification.
本研究的目的是确定蛙皮素与P物质在猫食管下括约肌(LES)处的相互作用。使用固定的灌注导管组件记录腔内压力。使用双极银 - 氯化银浆膜电极记录肌电活动。静脉注射蛙皮素可使LES压力呈剂量依赖性增加,并使电子计数的锋电位活动增加。阈剂量为10^(-7) g/kg,而最大剂量10^(-5) g/kg可使LES压力增加65.5±14.8 mmHg。神经拮抗剂河豚毒素使LES对蛙皮素的反应降低74.1%±7.9%(P<0.05),但对LES对P物质的反应无显著影响。双侧颈迷走神经切断术、阿托品、普萘洛尔或酚妥拉明均未抑制括约肌对蛙皮素的反应(P<0.10)。蛙皮素快速耐受消除了LES对蛙皮素的反应,但对P物质的反应无影响。相反,P物质快速耐受完全消除了LES对蛙皮素的反应(P<0.001)。P物质拮抗剂[D - Pro2, D - Trp7,9]P物质也显著抑制了LES对蛙皮素的反应(P<0.05)。用2.0 ml 0.1 N HCl酸化食管远端可使LES压力增加32.5±5.2 mmHg(P<0.02)。蛙皮素快速耐受抑制了LES对酸的反应(最大压力反应为4.7±2.1 mmHg,与对照酸反应相比P<0.01)。快速耐受技术对这些肽具有特异性,对LES对去氧肾上腺素、氨甲酰甲胆碱或五肽胃泌素的反应无影响。我们得出以下结论:(a)蛙皮素通过对肾上腺素能或胆碱能拮抗剂不敏感的非迷走神经途径增加猫LES压力;(b)蛙皮素可能参与介导猫LES对食管远端酸化反应的肠内途径;(c)P物质介导蛙皮素在LES处的作用,并且是LES对酸化反应中的一种神经递质。