Hemicholinium-3 derivatives A-4 and A-5 affect choline and acetylcholine metabolism.
The neuroblastoma-glioma hybrid cell (NG108-15) has a sodium-dependent, high-affinity choline transport system with a Km of 16.0 +/- 3.4 microM and a Vmax of 214.5 +/- 27.7 pmol/min/mg protein. A-4, A-5 and HC-3 produce dose-dependent inhibition of high-affinity choline transport in NG108-15 cells. Following 24 h exposure to approximately the EC50 of each inhibitor, no significant decrease was found in total choline accumulation or in choline incorporation into phosphatidylcholine. However, when additional inhibitor was added during the 24 h incubation, significant decreases in choline accumulation were produced by A-4 and A-5. Following 24 h exposure to each compound, only A-4 was able to significantly affect free choline content. In contrast, each inhibitor was able to significantly decrease acetylcholine content following 24 h exposure. Possible reasons for consistent decreases in acetylcholine versus minimal changes in choline metabolism will be discussed.
Sheff
K Y
KY
Department of Pharmacology, College of Medicine, University of Iowa, Iowa City 52242.
Yorek
M A
MA
Long
J P
JP
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D001713:Biphenyl Compounds / Q000494:pharmacology*; D002794:Choline / Q000378:metabolism*; D006426:Hemicholinium 3 / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010276:Parasympatholytics / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D001713:Biphenyl Compounds; D010276:Parasympatholytics; D010880:Piperidines; C057723:1,1'-((1,1'-biphenyl)-4,4'-diylbis(2-hydroxy-2,1-ethanediyl))bis(1,4-dimethylpiperidinium); D006426:Hemicholinium 3; C001771:4,4'-(2-(4-methylpiperidyl)-1-hydroxyethyl)biphenyl; D002794:Choline; D000109:Acetylcholine