Goldstein J L, Shapiro A B, Rao M C, Layden T J
Department of Medicine, University of Illinois Chicago.
Gastroenterology. 1991 Oct;101(4):1012-9. doi: 10.1016/0016-5085(91)90728-4.
In cystic fibrosis, cyclic adenosine monophosphate-mediated chloride secretion is abnormal in respiratory, small intestinal, and rectal mucosa. Calcium-mediated chloride secretion is also aberrant in CF small intestinal mucosa in cystic fibrosis, in contrast to the respiratory epithelia, where it appears to be normal. To determine whether this disparity between calcium- and cyclic adenosine monophosphate-mediated chloride secretion exists in cystic fibrosis rectal mucosa in vivo, transrectal potential difference was measured in age-matched adult cystic fibrosis subjects (n = 8) and control subjects (n = 9) in response to 10-minute luminal perfusions of bethanechol (1 mmol/L) or theophylline (5 mmol/L). In response to bethanechol, an initial (1-minute) negative change in potential difference (-1.4 +/- 1.1 mV; mean +/- SEM) was seen in control subjects, in contrast to a positive change in mean potential difference (+2.5 +/- 1.0 mV) in cystic fibrosis subjects (control vs. cystic fibrosis, P less than 0.05). After 1 minute, mean potential differences changes in both control and cystic fibrosis subjects were positive. Theophylline perfusion resulted in a significant (P less than 0.01) difference in potential difference response between groups; at 10 minutes, the potential difference became more negative (-3.6 +/- 1.4 mV) in control subjects and more positive in cystic fibrosis subjects (+3.9 +/- 1.4 mV). To determine whether second messenger-mediated potassium secretion contributed to the observed potential difference changes in response to bethanechol and theophylline, studies were repeated in the presence of barium chloride, a known blocker of potassium conductance. In the control group, barium chloride significantly enhanced the theophylline-induced negative potential difference change (P less than 0.05) and reduced the positive potential difference change seen with bethanechol alone. In subjects with cystic fibrosis, barium chloride completely abolished the previously seen positive potential difference change in response to either bethanechol or theophylline alone. These in vivo studies suggest that there is active potassium secretion in both control and cystic fibrosis rectal mucosa in response to cyclic adenosine monophosphate- and calcium-dependent secretagogues and that the magnitude of the potential difference changes attributable to barium-inhibitable potassium secretion is the same in cystic fibrosis and control subjects. In contrast, it appears that in cystic fibrosis rectal mucosa in vivo, calcium- as well as cyclic adenosine monophosphate-dependent chloride secretion is aberrant.
在囊性纤维化中，环磷酸腺苷介导的氯离子分泌在呼吸道、小肠和直肠黏膜中异常。与呼吸道上皮中钙介导的氯离子分泌似乎正常不同，在囊性纤维化患者的小肠黏膜中，钙介导的氯离子分泌也异常。为了确定在体内囊性纤维化直肠黏膜中钙介导和环磷酸腺苷介导的氯离子分泌之间是否存在这种差异，对年龄匹配的成年囊性纤维化患者（n = 8）和对照受试者（n = 9）进行经直肠电位差测量，以响应10分钟腔内灌注氨甲酰甲胆碱（1 mmol/L）或茶碱（5 mmol/L）。在灌注氨甲酰甲胆碱后，对照受试者出现了初始（1分钟）电位差的负向变化（-1.4±1.1 mV；平均值±标准误），而囊性纤维化患者的平均电位差出现正向变化（+2.5±1.0 mV）（对照与囊性纤维化，P<0.05）。1分钟后，对照和囊性纤维化患者的平均电位差变化均为正向。茶碱灌注导致两组间电位差反应存在显著差异（P<0.01）；在10分钟时，对照受试者的电位差变得更负（-3.6±1.4 mV），而囊性纤维化患者的电位差变得更正（+3.9±1.4 mV）。为了确定第二信使介导的钾离子分泌是否导致了观察到的对氨甲酰甲胆碱和茶碱的电位差变化，在存在已知的钾离子传导阻滞剂氯化钡的情况下重复进行研究。在对照组中，氯化钡显著增强了茶碱诱导的负向电位差变化（P<0.05），并减少了单独使用氨甲酰甲胆碱时观察到的正向电位差变化。在囊性纤维化患者中，氯化钡完全消除了之前单独使用氨甲酰甲胆碱或茶碱时观察到的正向电位差变化。这些体内研究表明，在对照和囊性纤维化直肠黏膜中，对环磷酸腺苷和钙依赖性促分泌剂均有活跃的钾离子分泌，并且在囊性纤维化和对照受试者中，归因于钡抑制性钾离子分泌的电位差变化幅度相同。相比之下，似乎在体内囊性纤维化直肠黏膜中，钙依赖性和环磷酸腺苷依赖性氯离子分泌均异常。
