Hemicholinium-3 derivatives A-4 and A-5 alter choline metabolism in NB41A3 neuroblastoma cells.
A-4, A-5 and HC-3 are experimental bis tertiary and quaternary amines which have been shown to be potent inhibitors of the sodium-dependent, high affinity choline uptake system. When incubated with neuroblastoma cells, experimental compounds A-4, A-5 and HC-3 inhibit choline metabolism. Over a 24-hr incubation, A-4, A-5 and HC-3 produced a significant decrease in total choline accumulation, choline incorporation into phospholipid and free choline content. However, despite decreases in choline incorporation into phospholipid, no change occurred in content of phosphatidylcholine. Treatment of cells with A-4, A-5 and HC-3 resulted in an increase in the incorporation of S-adenosyl-methionine into phosphatidylcholine. However, the incorporation of ethanolamine or serine into phosphatidylcholine was not increased. Phosphatidylcholine turnover was decreased in cells treated with A-4 and A-5. A-4, A-5 and HC-3 produce significant decreases in choline metabolism; however, the cells are able to maintain membrane integrity by decreasing turnover of phosphatidylcholine and increasing phosphatidylcholine synthesis through the methylation pathway. These studies suggest that the biological effects of A-4 and A-5 are independent of membrane perturbations.
Sheff
K Y
KY
Department of Pharmacology, College of Medicine, University of Iowa, Iowa City.
Yorek
M A
MA
Long
J P
JP
D000818:Animals; D001713:Biphenyl Compounds; D002794:Choline / Q000032:analysis / Q000378:metabolism*; D019856:Ethanolamine; D004983:Ethanolamines / Q000378:metabolism; D051379:Mice; D009447:Neuroblastoma / Q000378:metabolism; D010713:Phosphatidylcholines / Q000378:metabolism; D010743:Phospholipids / Q000032:analysis / Q000378:metabolism; D010880:Piperidines; D012436:S-Adenosylmethionine / Q000378:metabolism; D014407:Tumor Cells, Cultured
D001713:Biphenyl Compounds; D004983:Ethanolamines; D010713:Phosphatidylcholines; D010743:Phospholipids; D010880:Piperidines; C057723:1,1'-((1,1'-biphenyl)-4,4'-diylbis(2-hydroxy-2,1-ethanediyl))bis(1,4-dimethylpiperidinium); C001771:4,4'-(2-(4-methylpiperidyl)-1-hydroxyethyl)biphenyl; D019856:Ethanolamine; D012436:S-Adenosylmethionine; D002794:Choline