Comparison of cystic fibrosis transmembrane conductance regulator (CFTR) and ciliary beat frequency activation by the CFTR Modulators Genistein, VRT-532, and UCCF-152 in primary sinonasal epithelial cultures.

ABSTRACT: Pharmacologic activation of mucociliary clearance (MCC) represents an emerging therapeutic strategy for patients with chronic rhinosinusitis, even in the absence of congenital mutations of the CFTR gene. Drug discovery efforts have identified small molecules that activate the cystic fibrosis transmembrane conductance regulator (CFTR), including potentiators under development for treatment of cystic fibrosis.To evaluate the properties of CFTR modulators and their effects on ciliary beat frequency (CBF) in human sinonasal epithelium (HSNE).Primary HSNE cultures (wild type and F508del/F508del) were used to compare stimulation of CFTR-mediated Cl- conductance and CBF by the CFTR modulators genistein, VRT-532, and UCCF-152.Increase in CFTR-dependent anion transport and CBF.HSNE cultures were analyzed using pharmacologic manipulation of ion transport (change in short-circuit current [?ISC]) and high-speed digital imaging (CBF). Activation of CFTR-dependent anion transport was significantly different among agonists (P ?VRT-532, 8.1 [1.0] ?A/cm²?>?UCCF-152, 3.4 [1.4] ?A/cm² >?control, 0.7 [0.2] ?A/cm²; Tukey-Kramer P?

SUBMITTER: Conger BT 

PROVIDER: S-EPMC3933974 | biostudies-literature | 2013 Aug

REPOSITORIES: biostudies-literature