Levistre R, Lemnaouar M, Rybkine T, Béréziat G, Masliah J
URA CNRS 1283, Faculté de Médecine Saint Antoine, Université Pierre et Marie Curie, Paris, France.
Biochim Biophys Acta. 1993 Jun 19;1181(3):233-9. doi: 10.1016/0925-4439(93)90026-w.
Modification of chloride conductance by bradykinin in epithelial cells has been attributed to an activation of protein kinase A resulting from adenylcyclase stimulation by arachidonic acid cyclooxygenase products. The results presented here compare tracheal epithelial cell lines from one control and two cystic fibrosis patients which were immortalized by transfection with the SV40 large T oncogene. The three cell lines presented the same arachidonic acid content, turnover and mobilisation under basal conditions. Bradykinin stimulated the release of arachidonic acid and the synthesis of cyclooxygenase derivatives (mainly PGE2). The cell line from the cystic fibrosis patient bearing a phenylalanine 508 deletion, which is the major form of the disease, showed a higher bradykinin-induced arachidonic acid release than either control cells or cells from a patient presenting a minor form of the disease. This higher sensitivity suggests a dysregulation of phospholipase A2 stimulation in cystic fibrosis cells and was confirmed on non-immortalized tracheal epithelial cells in primary culture and on skin fibroblasts from patients bearing the same mutation. This defect is associated with a potentiation of cholera toxin pretreatment on cAMP content of delta F508 cell line. The impaired control of arachidonic acid release cannot be attributed to an increased number of bradykinin binding sites, since this increase was similar in the two cystic fibrosis cell lines.
缓激肽对上皮细胞氯离子电导的修饰作用被认为是由于花生四烯酸环氧化酶产物刺激腺苷酸环化酶导致蛋白激酶A激活所致。本文给出的结果比较了来自一名对照者和两名囊性纤维化患者的气管上皮细胞系，这些细胞系通过用SV40大T癌基因转染而永生化。在基础条件下，这三种细胞系呈现相同的花生四烯酸含量、周转率和动员情况。缓激肽刺激花生四烯酸的释放以及环氧化酶衍生物（主要是PGE2）的合成。携带苯丙氨酸508缺失（这是该疾病的主要形式）的囊性纤维化患者的细胞系，与对照细胞或患有该疾病次要形式的患者的细胞相比，显示出更高的缓激肽诱导的花生四烯酸释放。这种更高的敏感性表明囊性纤维化细胞中磷脂酶A2刺激的失调，并且在原代培养的非永生化气管上皮细胞以及携带相同突变的患者的皮肤成纤维细胞中得到证实。这种缺陷与霍乱毒素预处理对δF508细胞系cAMP含量的增强作用相关。花生四烯酸释放控制受损不能归因于缓激肽结合位点数量的增加，因为这种增加在两种囊性纤维化细胞系中是相似的。
