Effect of amiodarone and desethylamiodarone on choline uptake and phosphatidylcholine biosynthesis in cultured chick cardiac myocytes. 1990

S W Rabkin
University of British Columbia, Vancouver, Canada.

The objective of the study was to examine the hypothesis that amiodarone and its major metabolite desethylamiodarone alter choline uptake and metabolism in cardiac myocytes. Myocardial cells were obtained from 7-day-old chick embryos and were maintained in culture. Choline uptake, examined using [methyl 3H] choline, involves saturable and non-saturable processes. Amiodarone and desethylamiodarone at 10(-6) to 10(-4) M produced a significant (P less than 0.05) dose dependent reduction in choline uptake and inhibited the specific or carrier-mediated uptake process. The highest concentrations of each of these agents profoundly reduced choline uptake. Pulse chase experiments using [methyl 3H] choline showed that after a 2-h incubation with choline, about 85% of the label was recovered in phosphocholine, with the majority of the rest in phospholipid that was mainly phosphatidylcholine. Amiodarone and desethylamiodarone did not produce relevant alterations in choline metabolism namely phosphatidylcholine biosynthesis as neither drug altered the rate of disappearance of the label from phosphocholine or the appearance in phospholipid. Amiodarone but not desethylamiodarone produced a small but significant (P less than 0.05) increase in the amount of label that accumulated in CDP choline. These data demonstrate that amiodarone and desethylamiodarone decrease choline uptake into cardiac cells that may potentially be involved in either the mechanism of action or toxicity of amiodarone.

UI MeSH Term Description Entries
D007700 Kinetics The rate dynamics in chemical or physical systems.
D009206 Myocardium The muscle tissue of the HEART. It is composed of striated, involuntary muscle cells (MYOCYTES, CARDIAC) connected to form the contractile pump to generate blood flow. Muscle, Cardiac,Muscle, Heart,Cardiac Muscle,Myocardia,Cardiac Muscles,Heart Muscle,Heart Muscles,Muscles, Cardiac,Muscles, Heart
D010713 Phosphatidylcholines Derivatives of PHOSPHATIDIC ACIDS in which the phosphoric acid is bound in ester linkage to a CHOLINE moiety. Choline Phosphoglycerides,Choline Glycerophospholipids,Phosphatidyl Choline,Phosphatidyl Cholines,Phosphatidylcholine,Choline, Phosphatidyl,Cholines, Phosphatidyl,Glycerophospholipids, Choline,Phosphoglycerides, Choline
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D002642 Chick Embryo The developmental entity of a fertilized chicken egg (ZYGOTE). The developmental process begins about 24 h before the egg is laid at the BLASTODISC, a small whitish spot on the surface of the EGG YOLK. After 21 days of incubation, the embryo is fully developed before hatching. Embryo, Chick,Chick Embryos,Embryos, Chick
D002794 Choline A basic constituent of lecithin that is found in many plants and animal organs. It is important as a precursor of acetylcholine, as a methyl donor in various metabolic processes, and in lipid metabolism. Bursine,Fagine,Vidine,2-Hydroxy-N,N,N-trimethylethanaminium,Choline Bitartrate,Choline Chloride,Choline Citrate,Choline Hydroxide,Choline O-Sulfate,Bitartrate, Choline,Chloride, Choline,Choline O Sulfate,Citrate, Choline,Hydroxide, Choline,O-Sulfate, Choline
D006321 Heart The hollow, muscular organ that maintains the circulation of the blood. Hearts
D000638 Amiodarone An antianginal and class III antiarrhythmic drug. It increases the duration of ventricular and atrial muscle action by inhibiting POTASSIUM CHANNELS and VOLTAGE-GATED SODIUM CHANNELS. There is a resulting decrease in heart rate and in vascular resistance. Amiobeta,Amiodarex,Amiodarona,Amiodarone Hydrochloride,Amiohexal,Aratac,Braxan,Corbionax,Cordarex,Cordarone,Kordaron,L-3428,Ortacrone,Rytmarone,SKF 33134-A,Tachydaron,Trangorex,Hydrochloride, Amiodarone,L 3428,L3428,SKF 33134 A,SKF 33134A
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001693 Biological Transport, Active The movement of materials across cell membranes and epithelial layers against an electrochemical gradient, requiring the expenditure of metabolic energy. Active Transport,Uphill Transport,Active Biological Transport,Biologic Transport, Active,Transport, Active Biological,Active Biologic Transport,Transport, Active,Transport, Active Biologic,Transport, Uphill

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S W Rabkin
May 1988, Biochemistry and cell biology = Biochimie et biologie cellulaire,
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