Residual chloride secretion in intestinal tissue of ΔF508 homozygous twins and siblings with cystic fibrosis
Residual chloride secretion in intestinal tissue of ΔF508 homozygous twins and siblings with cystic fibrosis
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DOI：
10.1053/gast.2000.8524
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发表时间：
2000-07-01
期刊：
影响因子：
29.4
通讯作者：
Veeze, HJ
中科院分区：
文献类型：
--
作者：
Bronsveld, I;Mekus, F;Veeze, HJ
背景和目标：在囊性纤维化（CF）患者的肠道中，氯化物分泌的胆碱能刺激受损，然而，在轻度CF突变患者中观察到肠道氯化物分泌。本研究的目的是研究Delta F508纯合子CF患者肠道中的残留Cl-分泌，并检查囊性纤维化跨膜传导调节因子（CFTR）和替代Cl-传导的贡献。研究了CFTR基因型相同的双胞胎和兄弟姐妹，以确定CFTR以外的因素对氯分泌的影响。研究方法：在用4，4 '-二异硫氰基二苯乙烯-2，2'-二磺酸（DIDS）抑制交替氯离子传导之前和之后，通过应用Ca ~（2+）和环磷酸腺苷（cAMP）连接的激动剂来研究直肠组织的氯离子分泌。结果：在73%的患者中观察到cAMP介导的Cl-分泌，20%的患者表现出DIDS敏感的Ca 2+激活的Cl-分泌。这种DIDS敏感的替代氯电导仅见于对cAMP激动剂也有反应的CF患者。氯分泌更一致的单卵双胞胎比双卵对。结论：这些结果表明，CFTR介导的Cl-分泌在一个亚组的患者中的存在，这意味着一部分的Delta F508 CFTR可以在体内加工和功能作为一个氯离子通道在顶端膜的肠细胞。此外，相当数量的Delta F508纯合子患者在其肠上皮中表达CFTR以外的氯离子电导。
Background & Aims: Cholinergic stimulation of chloride secretion is impaired in the intestines of patients with cystic fibrosis (CF), However, intestinal chloride secretion has been observed in patients with mild CF mutations. The aim of this study was to investigate residual Cl- secretion in the intestine of Delta F508 homozygous CF patients, and examine the contribution of cystic fibrosis transmembrane conductance regulator (CFTR) and alternative Cl- conductances. Twins and siblings with identical CFTR genotypes were investigated to determine the impact of factors other than CFTR on chloride secretion. Methods: Chloride secretion in rectal tissue was investigated by applying Ca2+ and adenosine 3',5'-cyclic monophosphate (cAMP)linked agonists before and after the inhibition of alternative Cl- conductances with 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS). Results: cAMP-mediated Cl- secretion was observed in 73% of patients, and 20% showed DIDS-sensitive Ca2+-activated Cl- secretion. This DIDS-sensitive alternative chloride conductance was seen only in CF patients who also responded to cAMP agonists. Chloride secretion was more concordant within monozygous twins than within dizygous pairs. Conclusions: These results suggest the presence of CFTR-mediated Cl- secretion in a subgroup of patients, implying that a portion of Delta F508 CFTR can be processed in vivo and function as a chloride channel in the apical membrane of intestinal cells. Moreover, a considerable number of Delta F508 homozygous patients express chloride conductances other than CFTR in their intestinal epithelia.