Hemicholinium-3 derivatives A-4 and A-5 alter choline metabolism in NB41A3 neuroblastoma cells

Kimberly Y Sheff; Mark A Yorek; John P Long

doi:10.1016/S0022-3565(25)24804-2

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Hemicholinium-3 derivatives A-4 and A-5 alter choline metabolism in NB41A3 neuroblastoma cells

Journal article

Peer reviewed

Hemicholinium-3 derivatives A-4 and A-5 alter choline metabolism in NB41A3 neuroblastoma cells

Kimberly Y Sheff, Mark A Yorek and John P Long

The Journal of pharmacology and experimental therapeutics, Vol.257(1), pp.323-330

04/1991

DOI: 10.1016/S0022-3565(25)24804-2

PMID: 2019995

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Abstract

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.

Choline - metabolism

Ethanolamine

Phospholipids - analysis

Choline - analysis

Biphenyl Compounds

Phosphatidylcholines - metabolism

Animals

Ethanolamines - metabolism

Piperidines

Mice

Neuroblastoma - metabolism

Phospholipids - metabolism

Tumor Cells, Cultured

S-Adenosylmethionine - metabolism

Details

Title: Subtitle: Hemicholinium-3 derivatives A-4 and A-5 alter choline metabolism in NB41A3 neuroblastoma cells
Creators: Kimberly Y Sheff - Department of Pharmacology, College of Medicine, University of Iowa, Iowa City
Mark A Yorek
John P Long
Resource Type: Journal article
Publication Details: The Journal of pharmacology and experimental therapeutics, Vol.257(1), pp.323-330
DOI: 10.1016/S0022-3565(25)24804-2
PMID: 2019995
ISSN: 0022-3565
eISSN: 1521-0103
Grant note: AM-25295 / NIADDK NIH HHS NS-23785 / NINDS NIH HHS
Language: English
Date published: 04/1991
Academic Unit: Fraternal Order of Eagles Diabetes Research Center; Endocrinology and Metabolism; Internal Medicine
Record Identifier: 9984094703402771

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