INVIVO EVIDENCE OF ALTERED CHLORIDE BUT NOT POTASSIUM SECRETION IN CYSTIC-FIBROSIS RECTAL MUCOSA
INVIVO EVIDENCE OF ALTERED CHLORIDE BUT NOT POTASSIUM SECRETION IN CYSTIC-FIBROSIS RECTAL MUCOSA
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DOI：
10.1016/0016-5085(91)90728-4
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发表时间：
1991-10-01
期刊：
影响因子：
29.4
通讯作者：
LAYDEN, TJ
中科院分区：
文献类型：
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作者：
GOLDSTEIN, JL;SHAPIRO, AB;LAYDEN, TJ
在囊性纤维化中，环磷酸腺苷介导的氯分泌在呼吸道、小肠和直肠粘膜中异常。钙介导的氯化物分泌在囊性纤维化的CF小肠粘膜中也是异常的，与呼吸道上皮相反，在那里它似乎是正常的。为了确定体内囊性纤维化直肠粘膜中是否存在钙和环磷酸腺苷介导的氯化物分泌之间的这种差异，在年龄匹配的成人囊性纤维化受试者（n = 8）和对照受试者（n = 9）中测量经直肠电位差，以响应于10分钟的贝那普利（1 mmol/L）或茶碱（5 mmol/ L）的管腔灌注。在对氨甲酰胆碱的反应中，在对照受试者中观察到初始（1分钟）电位差的负变化（−1.4 ± 1.1 mV;平均值± SEM），而在囊性纤维化受试者中观察到平均电位差的正变化（+2.5 ± 1.0 mV）（对照vs.囊性纤维化，P< 0.05）。1分钟后，对照组和囊性纤维化受试者的平均电位差变化均为阳性。茶碱灌注导致组间电位差反应的显著差异（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），囊性纤维化受试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分泌是否有助于观察到的响应于氨甲酰胆碱和茶碱的电位差变化，在氯化钡（一种已知的钾传导阻滞剂）存在下重复研究。在对照组中，氯化钡显著增强茶碱引起的负电位差变化（P< 0.05），并减少单独氨甲酰胆碱引起的正电位差变化（P< 0.05）。在囊性纤维化的受试者中，氯化钡完全消除了先前观察到的单独对氨甲酰胆碱或茶碱的正电位差变化。这些在体内的研究表明，有积极的钾分泌在控制和囊性纤维化直肠粘膜响应环磷酸腺苷和钙依赖性促分泌素和电位差的变化幅度的变化归因于钡可吸收的钾分泌是相同的囊性纤维化和对照组。相反，在囊性纤维化直肠粘膜体内，钙和环磷酸腺苷依赖性氯分泌似乎是异常的。
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< 0.05). After 1 minute, mean potential difference changes in both control and cystic fibrosis subjects were positive. Theophylline perfusion resulted in a significant (P< 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< 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.