Application of X-ray microanalysis to the study of drug uptake in cell culture.
X-ray microanalysis has been used previously to study the accumulation of iodine in alveolar macrophages of rats treated with the iodinated drug, amiodarone. Due to metabolism of the drug in vivo, primarily to desethylamiodarone, it was not possible to identify the source of the iodine signal. In the present study we have utilized primary cell cultures of alveolar macrophages to study the intracellular accumulation of each of these drug species in vitro. Neither drug is metabolized by these cells in culture, permitting characterization of the accumulation of each independent of the other. Cells were incubated with equimolar concentrations of either amiodarone or desethylamiodarone for 42 hr, and X-ray microanalysis of freeze-dried cryosections of cells was used to quantify accumulation by monitoring the iodine signal associated with each drug. For both drug exposures, the highest iodine content was present in amorphous bodies and dense granules, consistent with the pattern following in vivo exposure. Higher levels of desethylamiodarone, compared to amiodarone, were measured in all compartments of the cells. The results of the in vitro investigation further demonstrate the utility of X-ray microanalysis in the study of the cellular response to amiodarone and desethylamiodarone.
Reasor
M J
MJ
Department of Pharmacology, West Virginia University Health Sciences Center, Morgantown 26506.
Lee
P
P
Kirk
R G
RG
D000638:Amiodarone / Q000031:analogs & derivatives* / Q000032:analysis / Q000493:pharmacokinetics* / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D004577:Electron Probe Microanalysis; D007455:Iodine / Q000032:analysis / Q000493:pharmacokinetics / Q000494:pharmacology; D008264:Macrophages / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D015388:Organelles / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000166:cytology; D051381:Rats; D011916:Rats, Inbred F344
D007455:Iodine; C036116:desethylamiodarone; D000638:Amiodarone