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.

Progesterone Downregulates Oestrogen-Induced Expression of CFTR and SLC26A6 Proteins and mRNA in Rats’ Uteri

“…To the best of our knowledge, this is the first report on the acute suppression by progesterone on CFTR expression in vivo in steroid replaced ovariectomized rats as well as under a high endogenous P level, thus supporting the previous in vitro observation by Mularoni et al (1995) [25]. Progesterone effect on CFTR expression could be mediated via genomic pathway possibly via CFTR gene suppression, apart from an indirect inhibition of CFTR activities via the activation of epithelial Na + channel (ENaC) as ENaC has been shown to be a negative regulator of CFTR [29]. We need to further confirm this by administering a progesterone receptor blocker, mifepristone.…”

Increased Cystic Fibrosis Transmembrane Conductance Regulators Expression and Decreased Epithelial Sodium Channel Alpha Subunits Expression in Early Abortion: Findings from a Mouse Model and Clinical Cases of Abortion

“…Overexpression of CFTR and inadequate expression of ENaC-α was observed in the decidua from abortion-prone mice and women who had a miscarriage. CFTR have shown to be a negative regulator of ENaC in mouse endometrial epithelium which is important for liquid microenvironment during peri-implantation [18]. The abnormal expression of CFTR and ENaC-α might disrupt the cellular microenvironment that is harmful for embryo implantation or maintain of pregnancy; or might result from degeneration or necrosis of decidua as a consequence of miscarriage.…”

Lower Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Promotes the Proliferation and Migration of Endometrial Carcinoma

“…Chan et al found that CFTR might restrain the activity of the glandular epithelial cells sodium ion channel inside mouse endometrium and directly mediate the secretion of HCO-, which would impact the pH value of the uterine cavity fluid [ 7 ]. In addition, if the endometrial glandular epithelium lacked CFTR protein, it would obviously restrain the capacitation of sperm, and lead to sterility [ 7 , 8 ].…”

“…Chan et al found that CFTR might restrain the activity of the glandular epithelial cells sodium ion channel inside mouse endometrium and directly mediate the secretion of HCO-, which would impact the pH value of the uterine cavity fluid [ 7 ]. In addition, if the endometrial glandular epithelium lacked CFTR protein, it would obviously restrain the capacitation of sperm, and lead to sterility [ 7 , 8 ]. The expression of CFTR mRNA and protein are observed in endometrial glandular epithelial cells of women’s menstrual cycle, and the expression is generally thought to change with the menstrual cycle: in the later proliferative stage there is a strengthening of CFTR expression, whereas the CFTR expression and the local control in the secretory phase might participate in the regulation and control of blastocyst implantation.…”