A role for cftr in human autosomal dominant polycystic kidney
disease.
Hanaoka, Kazushige, Olivier Devuyst, Erik M. Schwiebert, Patricia D.
Wilson, and William B. Guggino.
Department of Physiology and Division of Nephrology, The Johns
Hopkins University, School of Medicine, Baltimore, Maryland 21205
APStracts 2:0346C, 1995.
Human autosomal dominant polycystic kidney disease (ADPKD) is the most
common lethal dominant hereditary disorder characterized by enormous
renal enlargement and the development of multiple cysts originating
from nephrons. We investigated the pathogenesis of cyst formation in
ADPKD by using patch-clamp and immunocytochemical techniques. cAMP
-activated Cl- currents are present in primary cultures of ADPKD cells
and have characteristics such as a linear I-V relation, insensitivity
to 4, 4-diisothiocyanostilbene-2, 2-disulfonic acid (DIDS),
sensitivity to glybenclamide and diphenylamine carboxylic acid (DPC)
and an anion selectivity sequence of Br- > Cl- > I- >
Glutamate-, all of which are identical to CFTR. Using CFTR antibodies
raised against the regulatory and first nucleotide binding domains,
CFTR was detected in primary cultures of ADPKD cells. Similar results
were obtained in vivo in cyst-lining epithelial cells in ADPKD
kidneys where staining was seen associated with the apical membrane
regions. These data indicate that CFTR Cl- channel exists in apical
membranes of ADPKD cells and may play an important role in cyst
formation or enlargement.
Received 7 July 1995; accepted in final form 25 September 1995
APS Manuscript Number C408-5.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 31 October 95