| 9916004 |
Chan LN, Chung YW, Leung PS, Liu CQ, Chan HC: Activation of an adenosine 3',5'-cyclic monophosphate-dependent Cl- conductance in response to neurohormonal stimuli in mouse endometrial epithelial cells: the role of cystic fibrosis transmembrane conductance regulator. Biol Reprod. 1999 Feb;60(2):374-80.
Previous studies have demonstrated that Cl- secretion by the mouse endometrial epithelium is under neurohormonal influence. The present study characterized the Cl- conductance activated by a number of agonists in the mouse endometrial epithelial cells using the whole-cell voltage-clamp technique. Adrenaline (1 microM), prostaglandin (PG) E2 (5-10 microM), and PGF2alpha (100 microM) activated a whole-cell current that exhibited a linear I-V relationship as well as time- and voltage-independent characteristics. However, the current magnitude varied with different agonists. The agonist-activated current could be mimicked by an adenylate cyclase activator, forskolin (10 microM), and suppressed by an adenylate cyclase inhibitor, MDL12330A, suggesting the involvement of cAMP. Current characteristics remained the same after cation replacement, leaving Cl- as the major permeant ion species in the solutions. The reversal potential of the agonist-induced current was close to the equilibrium potential of Cl- in the presence of a Cl- gradient, indicating the activation of Cl- conductance. The agonist-induced current was inhibited by the Cl- channel blocker diphenylamine 2,2'-dicarboxylic acid (DPC), but not by the Cl- channel blocker 4,4'-diisothiocyanatostibene-2, 2'-disulfonic acid (DIDS). The anion selectivity sequence of the current was NO3-> Br-> Cl-> I-. The observed electrophysiological properties of the agonist-induced Cl- conductance were consistent with those reported for the cystic fibrosis transmembrane conductance regulator (CFTR), a cAMP-activated Cl- channel expressed in many epithelia. The expression of CFTR in the mouse endometrial cells was also demonstrated by Western blot analysis. It appears that neurohormonal regulation of the uterine fluid in the mouse endometrium converges on the cAMP-activated Cl- channel, presumably CFTR. |
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