Cystic Fibrosis Transmembrane Conductance Regulator Genotype, Not Circulating Catecholamines, Influences Cardiovascular Function in Patients with Cystic Fibrosis.

Background: Cystic fibrosis (CF) is a genetic disease affecting multiple organ systems of the body and is characterized by mutation in the gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR). Previous work has shown that a single dose of aβ-agonist increases cardiac output (Q) and stroke volume (SV) and decreases systemic vascular resistance (SVR) in healthy subjects. This effect is attenuated in patients with CF; however, the mechanism is unknown.

Carvedilol binding to β2-adrenergic receptors inhibits CFTR-dependent anion secretion in airway epithelial cells.

Carvedilol functions as a nonselective β-adrenergic receptor (AR)/α1-AR antagonist that is used for treatment of hypertension and heart failure. Carvedilol has been shown to function as an inverse agonist, inhibiting G protein activation while stimulating β-arrestin-dependent signaling and inducing receptor desensitization. In the present study, short-circuit current (Isc) measurements using human airway epithelial cells revealed that, unlike β-AR agonists, which increase Isc, carvedilol decreases basal and 8-(4-chlorophenylthio)adenosine 3',5'-cyclic monophosphate-stimulated current.

Agonist binding to β-adrenergic receptors on human airway epithelial cells inhibits migration and wound repair.

Human airway epithelial cells express β-adrenergic receptors (β-ARs), which regulate mucociliary clearance by stimulating transepithelial anion transport and ciliary beat frequency. Previous studies using airway epithelial cells showed that stimulation with isoproterenol increased cell migration and wound repair by a cAMP-dependent mechanism. In the present study, impedance-sensing arrays were used to measure cell migration and epithelial restitution following wounding of confluent normal human bronchial epithelial (NHBE) and Calu-3 cells by electroporation.

K(Ca)3.1 channels facilitate K+ secretion or Na+ absorption depending on apical or basolateral P2Y receptor stimulation.

Human mammary epithelial (HME) cells express several P2Y receptor subtypes located in both apical and basolateral membranes. Apical UTP or ATP-γ-S stimulation of monolayers mounted in Ussing chambers evoked a rapid, but transient decrease in short circuit current (I(sc)), consistent with activation of an apical K+ conductance. In contrast, basolateral P2Y receptor stimulation activated basolateral K+ channels and increased transepithelial Na+ absorption.