Pharmacological modulation of ion transport across wild- type and DF508 CFTR-expressing human bronchial epithelia
نویسندگان
چکیده
Devor, Daniel C., Robert J. Bridges, and Joseph M. Pilewski. Pharmacological modulation of ion transport across wild-type and DF508 CFTR-expressing human bronchial epithelia. Am J Physiol Cell Physiol 279: C461–C479, 2000.—Forskolin, UTP, 1-ethyl-2-benzimidazolinone (1EBIO), NS004, 8-methoxypsoralen (Methoxsalen; 8-MOP), and genistein were evaluated for their effects on ion transport across primary cultures of human bronchial epithelium (HBE) expressing wild-type (wt HBE) and DF508 (DF-HBE) cystic fibrosis transmembrane conductance regulator. In wt HBE, the baseline short-circuit current (Isc) averaged 27.0 6 0.6 mA/cm (n 5 350). Amiloride reduced this Isc by 13.5 6 0.5 mA/cm (n 5 317). In DF-HBE, baseline Isc was 33.8 6 1.2 mA/cm (n 5 200), and amiloride reduced this by 29.6 6 1.5 mA/cm (n 5 116), demonstrating the characteristic hyperabsorption of Na associated with cystic fibrosis (CF). In wt HBE, subsequent to amiloride, forskolin induced a sustained, bumetanide-sensitive Isc (DIsc 5 8.4 6 0.8 mA/cm ; n 5 119). Addition of acetazolamide, 5-(N-ethyl-N-isopropyl)-amiloride, and serosal 4,49-dinitrostilben-2,29-disulfonic acid further reduced Isc, suggesting forskolin also stimulates HCO3 2
منابع مشابه
Proinflammatory cytokine secretion is suppressed by TMEM16A or CFTR channel activity in human cystic fibrosis bronchial epithelia
Cystic fibrosis (CF) is caused by the functional expression defect of the CF transmembrane conductance regulator (CFTR) chloride channel at the apical plasma membrane. Impaired bacterial clearance and hyperactive innate immune response are hallmarks of the CF lung disease, yet the existence of and mechanism accounting for the innate immune defect that occurs before infection remain controversia...
متن کاملPharmacological modulation of ion transport across wild-type and DeltaF508 CFTR-expressing human bronchial epithelia.
Forskolin, UTP, 1-ethyl-2-benzimidazolinone (1-EBIO), NS004, 8-methoxypsoralen (Methoxsalen; 8-MOP), and genistein were evaluated for their effects on ion transport across primary cultures of human bronchial epithelium (HBE) expressing wild-type (wt HBE) and DeltaF508 (DeltaF-HBE) cystic fibrosis transmembrane conductance regulator. In wt HBE, the baseline short-circuit current (I(sc)) averaged...
متن کاملCYSTIC FIBROSIS Sildenafil (Viagra) corrects DF508-CFTR location in nasal epithelial cells from patients with cystic fibrosis
Background: Most patients with cystic fibrosis (CF) have a DF508 mutation resulting in abnormal retention of mutant gene protein (DF508-CFTR) within the cell. This study was undertaken to investigate DF508-CFTR trafficking in native cells from patients with CF with the aim of discovering pharmacological agents that can move DF508-CFTR to its correct location in the apical cell membrane. Method:...
متن کاملLoss of Anion Transport without Increased Sodium Absorption Characterizes Newborn Porcine Cystic Fibrosis Airway Epithelia
Defective transepithelial electrolyte transport is thought to initiate cystic fibrosis (CF) lung disease. Yet, how loss of CFTR affects electrolyte transport remains uncertain. CFTR⁻(/)⁻ pigs spontaneously develop lung disease resembling human CF. At birth, their airways exhibit a bacterial host defense defect, but are not inflamed. Therefore, we studied ion transport in newborn nasal and trach...
متن کاملRegulation of CFTR chloride channel trafficking by Nedd4-2: role of SGK1
Introduction: The cystic fibrosis transmembrane conductance regulator (CFTR) chloride (Cl−) channel is an essential component of epithelial Cl− transport systems in many organs. CFTR is mainly expressed in the lung and other tissues, such as testis, duodenum, trachea and kidney. The ubiquitin ligase neural precursor cells expressed developmentally down-regulated protein 4-2 (Nedd4-2...
متن کامل