title: Renal effects of glibenclamide in cystic fibrosis mice.
abstract: In vitro studies have shown that glibenclamide sensitivity is conferred upon Kir 1.1 K(+) channels when they are co-expressed with the cystic fibrosis transmembrane conductance regulator (CFTR). In rats, glibenclamide acts as a K(+)-sparing diuretic by a mechanism that involves blockade of Kir 1.1 channels in the distal nephron. To test whether interaction between Kir 1.1 and CFTR is required to mediate the renal effects of glibenclamide (15 mg/kg), clearance experiments were performed comparing wild type (WT) and Cftr(tm2cam) Delta F508 cystic fibrosis (CF) mice. Glibenclamide treatment was associated with an equivalent diuresis in both WT and CF mice. Glibenclamide was K(+)-sparing in both genotypes with no significant change in urinary K(+) excretion observed. That glibenclamide was an effective K(+)-sparing diuretic in CF animals suggests that CFTR expression is not a requirement to mediate its renal actions in mice.
authors.affiliation: Department of Biomedical Science, University of Sheffield, United Kingdom.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Kibble
authors.affiliation: Department of Biomedical Science, University of Sheffield, United Kingdom.
authors.forename: Andrew
authors.initials: A
authors.lastname: Neal
authors.affiliation: Department of Biomedical Science, University of Sheffield, United Kingdom.
authors.forename: Stanley
authors.initials: S
authors.lastname: White
authors.affiliation: School of Biological Sciences, University of Manchester, United Kingdom.
authors.forename: Roger
authors.initials: R
authors.lastname: Green
authors.affiliation: The Sheffield Children's Hospital, Sheffield, United Kingdom.
authors.forename: Steve
authors.initials: S
authors.lastname: Evans
authors.affiliation: The Sheffield Children's Hospital, Sheffield, United Kingdom.
authors.forename: Christopher
authors.initials: C
authors.lastname: Taylor
mesh_terms: D000818:Animals; D003550:Cystic Fibrosis / Q000503:physiopathology* / Q000652:urine; D004232:Diuretics / Q000494:pharmacology*; D005905:Glyburide / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects*; D051379:Mice; D011188:Potassium / Q000652:urine; D012016:Reference Values
chemical_list: D004232:Diuretics; D011188:Potassium; D005905:Glyburide