The chloride channel blocker anthracene 9-carboxylate inhibits fatty acid incorporation into phospholipid in cultured human airway epithelial cells.
This study investigated whether making epithelial cell membranes impermeable to Cl- movement affects incorporation of fatty acids into membrane constituents. Epithelial cells were isolated from human nasal polyps, cultured for 5-7 days, and used to test the effect of anthracene 9-carboxylate (9-AC), known to inhibit Cl- conductance across the epithelial membrane, on the incorporation and desaturation of [1-14C]linoleic acid (C18:2,n-6) in experiments of up to 4 h duration. 9-AC (5 mM) reduced C18:2,n-6 incorporation into phospholipid by 60-70%, and increased incorporation of C18:2,n-6 into triacylglycerol by 50-100%. The decrease in C18:2,n-6 incorporation into phospholipid was rapid and dependent on the concentration of 9-AC. Substitution of extracellular Cl- with gluconate significantly decreased C18:2,n-6 incorporation into phospholipid, suggesting that the effect of 9-AC may occur by inhibiting Cl- conductance. Lipid analysis of cells exposed to 50 microM-C18:2 revealed that, as a consequence of the effect of 9-AC, the level of C18:2,n-6 in cell membrane phospholipid was significantly lowered. The relative rate of C18:2,n-6 desaturation was not apparently changed by 9-AC. These data suggest that Cl- conductance may play a role in fatty acid incorporation into epithelial cell membrane phospholipids.
Kang
J X
JX
Nutrition and Metabolism Research Group, University of Alberta, Edmonton, Canada.
Man
S F
SF
Brown
N E
NE
Labrecque
P A
PA
Clandinin
M T
MT
D000584:Amiloride / Q000494:pharmacology; D000873:Anthracenes / Q000494:pharmacology*; D002478:Cells, Cultured; D018118:Chloride Channels; D002712:Chlorides / Q000378:metabolism; D003550:Cystic Fibrosis / Q000378:metabolism; D004553:Electric Conductivity; D004848:Epithelium / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D019787:Linoleic Acid; D008041:Linoleic Acids / Q000378:metabolism; D008565:Membrane Proteins / Q000037:antagonists & inhibitors*; D009297:Nasal Mucosa / Q000378:metabolism*; D009298:Nasal Polyps; D010743:Phospholipids / Q000378:metabolism*; D014280:Triglycerides / Q000378:metabolism; D014700:Verapamil / Q000494:pharmacology
D000873:Anthracenes; D018118:Chloride Channels; D002712:Chlorides; D005227:Fatty Acids; D008041:Linoleic Acids; D008565:Membrane Proteins; D010743:Phospholipids; D014280:Triglycerides; C010030:9-anthroic acid; D000584:Amiloride; D019787:Linoleic Acid; D014700:Verapamil