Effect of IBMX and alkaline phosphatase inhibitors on Cl2 secretion in G551D cystic fibrosis mutant mice
نویسندگان
چکیده
STEPHEN N. SMITH,1 STEPHEN J. DELANEY,2 JULIA R. DORIN,3 RAYMOND FARLEY,1 DUNCAN M. GEDDES,1 DAVID J. PORTEOUS,3 BRANDON J. WAINWRIGHT,2 AND ERIC W. F. W. ALTON1 1Ion Transport Unit, National Heart and Lung Institute, London SW3 6LR, United Kingdom; 2Department for Molecular and Cellular Biology, University of Queensland, Brisbane 4072, Australia; and 3Medical Research Council Human Genetics Unit, Western General Hospital, Edinburgh EH4 2XU, United Kingdom
منابع مشابه
Effect of IBMX and alkaline phosphatase inhibitors on Cl- secretion in G551D cystic fibrosis mutant mice.
Some cystic fibrosis transmembrane conductance regulator (CFTR) mutations, such as G551D, result in a correctly localized Cl- channel at the cell apical membrane, albeit with markedly reduced function. Patch-clamp studies have indicated that both phosphatase inhibitors and 3-isobutyl-1-methylxanthine (IBMX) can induce Cl- secretion through the G551D mutant protein. We have now assessed whether ...
متن کاملCystic fibrosis mice carrying the missense mutation G551D replicate human genotype-phenotype correlations.
We have generated a mouse carrying the human G551D mutation in the cystic fibrosis transmembrane conductance regulator gene (CFTR) by a one-step gene targeting procedure. These mutant mice show cystic fibrosis pathology but have a reduced risk of fatal intestinal blockage compared with 'null' mutants, in keeping with the reduced incidence of meconium ileus in G551D patients. The G551D mutant mi...
متن کاملDifferential Metabolic Effects of Novel Cilostamide Analogs, Methyl Carbostiryl Derivatives, on Mouse and Hyperglycemic Rat
Objective(s) PDE3 has a functional role in insulin secretion and action. We investigated the metabolic effects of new synthetic PDE3 inhibitors (mc1, mc2, mc5 and mc6), on mice and hyperglycemic rat. Materials and Methods The test compound or solvent was injected subcutaneously to mice, for 7 days. On day 8, blood and liver samples were obtained. In hyperglycemic rat, 0.5 g/kg glucose with o...
متن کاملCystic Fibrosis Transmembrane Conductance Regulator (CFTR) Potentiators Protect G551D but Not ΔF508 CFTR from Thermal Instability
The G551D cystic fibrosis transmembrane conductance regulator (CFTR) mutation is associated with severe disease in ∼5% of cystic fibrosis patients worldwide. This amino acid substitution in NBD1 results in a CFTR chloride channel characterized by a severe gating defect that can be at least partially overcome in vitro by exposure to a CFTR potentiator. In contrast, the more common ΔF508 mutation...
متن کاملAlterations in blood leukocytes of G551D-bearing cystic fibrosis patients undergoing treatment with ivacaftor.
BACKGROUND Ivacaftor improves clinical outcome by potentiation of mutant G551D CFTR. Due to the presence of CFTR in monocytes and polymorphonuclear neutrophils (PMNs), we hypothesized that ivacaftor may impact leukocyte activation. METHODS We examined blood leukocytes from G551D CF subjects prior to and at one and six months after receiving ivacaftor. Blood leukocytes from ivacaftor-naïve G55...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
دوره شماره
صفحات -
تاریخ انتشار 1998