title: Inhibition of amiloride-sensitive Na(+) absorption by activation of CFTR in mouse endometrial epithelium.
abstract: Previous studies have demonstrated amiloride-sensitive Na(+) absorption under basal conditions and cystic fibrosis transmembrane conductance regulator (CFTR)-mediated Cl(-) secretion following neurohormonal stimulation in the mouse endometrial epithelium. The present study investigated the inhibition of amiloride-sensitive Na(+) absorption accompanying activation of CFTR in the mouse endometrium using the short-circuit current ( I(sc)) technique. RT-PCR demonstrated the co-expression of CFTR and epithelial Na(+) channels (ENaC) in primary cultured mouse endometrial epithelia and cultured endometrial monolayers exhibited a basal amiloride-sensitive I(sc) of 5.4 +/- 0.6 microA/cm(2). The amiloride-sensitive current fell to 3.1 +/- 0.5 microA/cm(2) after stimulation with forskolin. When the possible contribution of Na(+) absorption to the I(sc) was eliminated by amiloride (1 microM) or Na(+) replacement, the forskolin-induced I(sc) was not reduced, but rather increased significantly compared with that in the absence of amiloride or in Na(+)-containing solutions ( P < 0.02), indicating that the forskolin-induced I(sc) was mediated by Cl(-) secretion, portion of which may be masked by concurrent inhibition of basal Na(+) absorption if the contribution of Na(+) is not eliminated. When the contribution of Cl(-) to the I(sc) was eliminated by diphenylamine 2,2'-dicarboxylic acid (DPC, 2 mM) or Cl(-) replacement, forskolin now decreased, rather than increased the I(sc), demonstrating the inhibition of Na(+) absorption upon stimulation. Our data suggest an interaction between CFTR and ENaC, which may be the underlying mechanism for balancing Na(+) absorption and Cl(-) secretion across the mouse endometrial epithelium.
authors.affiliation: Epithelial Cell Biology Research Centre, Department of Physiology, The Chinese University of Hong Kong, Shatin, Hong Kong.
authors.forename: L N
authors.initials: LN
authors.lastname: Chan
authors.forename: X F
authors.initials: XF
authors.lastname: Wang
authors.forename: L L
authors.initials: LL
authors.lastname: Tsang
authors.forename: S C
authors.initials: SC
authors.lastname: So
authors.forename: Y W
authors.initials: YW
authors.lastname: Chung
authors.forename: C Q
authors.initials: CQ
authors.lastname: Liu
authors.forename: H C
authors.initials: HC
authors.lastname: Chan
mesh_terms: D000584:Amiloride / Q000494:pharmacology*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002712:Chlorides / Q000378:metabolism; D005576:Colforsin / Q000494:pharmacology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics / Q000378:metabolism*; D004232:Diuretics / Q000494:pharmacology*; D004717:Endometrium / Q000166:cytology / Q000378:metabolism*; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D053503:Epithelial Sodium Channels; D005260:Female; D015870:Gene Expression / Q000502:physiology; D051379:Mice; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012964:Sodium / Q000378:metabolism*; D015222:Sodium Channels / Q000235:genetics / Q000378:metabolism
chemical_list: D002712:Chlorides; D004232:Diuretics; D053503:Epithelial Sodium Channels; D012333:RNA, Messenger; D015222:Sodium Channels; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D005576:Colforsin; D000584:Amiloride; D012964:Sodium