ATP-activated basolateral Na+/H+ exchange in human normal and cystic fibrosis airway epithelium.
This study investigated the distribution (apical/basolateral membrane) of Na+/H+ exchange in human nasal epithelial cell monolayers from cystic fibrosis (CF) and non-CF individuals. Monolayers of non-CF and CF preparations were loaded with the pH probe 2',7'-bis(carboxyethyl)-5(6)- carboxyfluorescein, and intracellular pH (pH1) was measured with a microfluorimeter. In nominally HCO3(-)-free NaCl Ringer solution, basal pHi values in non-CF and CF monolayers were essentially identical (approximately 7.1). When cells were acid loaded (NH4+ prepulse), subsequent alkalinization of non-CF and CF cell monolayers required serosal Na+ and was blocked by serosal, but not mucosal, amiloride (500 microM). In the presence of extracellular Na+, initial rates (delta pHi/min) of recovery from an acid load in non-CF and CF preparations were statistically identical (approximately 0.08). Pretreatment of monolayers with ATP (100 microM) or phorbol 12-myristate 13-acetate (PMA; 100 nM) caused initial rates of recovery to increase by twofold over control values in both preparations. These data provide evidence in support for an ATP- and PMA-activated Na+/H+ exchanger located at the basolateral surface of airway epithelia.
Paradiso
A M
AM
Department of Medicine, University of North Carolina, Chapel Hill 27599, USA.
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000293:Adolescent; D000328:Adult; D000643:Ammonium Chloride / Q000494:pharmacology; D002462:Cell Membrane / Q000502:physiology; D016764:Cell Polarity; D002478:Cells, Cultured; D002648:Child; D003550:Cystic Fibrosis / Q000378:metabolism / Q000503:physiopathology*; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008297:Male; D009297:Nasal Mucosa / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology*; D009550:Nigericin / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D012016:Reference Values; D017923:Sodium-Hydrogen Exchangers / Q000187:drug effects / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D017923:Sodium-Hydrogen Exchangers; D000643:Ammonium Chloride; D011189:Potassium Chloride; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000255:Adenosine Triphosphate; D013755:Tetradecanoylphorbol Acetate; D009550:Nigericin