O'Loughlin E V, Hunt D M, Bostrom T E, Hunter D, Gaskin K J, Gyory A, Cockayne D J
Department of Gastroenterology, New Children's Hospital, Westmead, New South Wales, Australia.
Gastroenterology. 1996 Feb;110(2):411-8. doi: 10.1053/gast.1996.v110.pm8566587.
BACKGROUND & AIMS: Cystic fibrosis transmembrane conductance regulator (CFTR) is an adenosine 3',5'-cyclic monophosphate-dependent chloride channel that is defective in cystic fibrosis. The aims of this study were to determine if defective apical chloride secretion in the intestine of patients with cystic fibrosis alters the intracellular electrolyte milieu and to examine the geographical localization of CFTR in the normal intestine.
The content of intracellular elements was assessed in cryosections using energy-dispersive x-ray microanalysis, and CFTR was identified by immunocytochemistry using commercially available antibodies.
Cystic fibrosis jejunum had a significantly lower Na+ content, higher K+ and Cl- content, and higher potassium/phosphorus ratio in both villus and crypt regions. Incubation of normal jejunum with the phosphodiesterase inhibitor 3-isobutyl-1-methyl-xanthine (300 mumol/L) resulted in decreased K+ and Cl- content in both crypt and villus regions, indicative of Cl- secretion. CFTR was identified on the surface of normal villus and crypt enterocytes but not in cystic fibrosis samples.
Defective apical chloride channels in cystic fibrosis result in alterations in the intracellular electrolyte milieu. The microanalysis observations and immunocytochemical studies imply a role for villus enterocytes in human intestinal chloride secretion.
囊性纤维化跨膜传导调节因子（CFTR）是一种依赖于3'，5'-环磷酸腺苷的氯离子通道，在囊性纤维化中存在缺陷。本研究的目的是确定囊性纤维化患者肠道顶端氯离子分泌缺陷是否会改变细胞内电解质环境，并研究CFTR在正常肠道中的地理定位。
使用能量色散X射线微分析法评估冷冻切片中细胞内元素的含量，并使用市售抗体通过免疫细胞化学鉴定CFTR。
囊性纤维化空肠在绒毛和隐窝区域的Na+含量显著降低，K+和Cl-含量升高，钾/磷比值升高。用磷酸二酯酶抑制剂3-异丁基-1-甲基黄嘌呤（300μmol/L）孵育正常空肠导致隐窝和绒毛区域的K+和Cl-含量降低，表明有氯离子分泌。在正常绒毛和隐窝肠上皮细胞表面鉴定出CFTR，但在囊性纤维化样本中未鉴定出。
囊性纤维化中顶端氯离子通道缺陷导致细胞内电解质环境改变。微量分析观察和免疫细胞化学研究表明绒毛肠上皮细胞在人体肠道氯离子分泌中起作用。
