Subcellular distribution of the antidepressant drug desipramine in cultured human fibroblasts after chronic administration. Drug-effect on the subcellular distribution of accumulated phospholipids.
Desipramine (DMI) is an important antidepressant drug and a lysosomotropic substance. In cultured fibroblasts it interferes with lysosomal functions, e.g. phospholipid degradation. Chronic exposure of cells with DMI induces storage of phospholipids. Subcellular fractionations of cultured human fibroblasts that had been exposed to a short pulse of 3H-DMI showed accumulation of DMI in two acidic compartments, one of high density represented the lysosomes and one of much lower density may contain pinosomes. In chronically exposed cells DMI accumulated in the subcellular fractions of lower density only. DMI induced an important shift of lysosomal enzymes from vesicles of high density to the ones of lower density. Phospholipids were accumulating in those vesicles of lower density as well as in the fractions that contained plasma membranes. DMI also accumulated in one part of the Golgi vesicles of acute and chronically exposed cells. In the latter phospholipids and arylsulfatase A activity were also accumulating. DMI possibly interferes with membrane recycling. This eventually could induce changes in phospholipid content and composition in the plasma membrane which may have important implications for membrane functions.
D002458:Cell Fractionation; D002478:Cells, Cultured; D003600:Cytosol / Q000378:metabolism; D003891:Desipramine / Q000378:metabolism* / Q000494:pharmacology; D005347:Fibroblasts / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D008247:Lysosomes / Q000378:metabolism; D008563:Membrane Lipids / Q000032:analysis; D008861:Microsomes / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism*
D008563:Membrane Lipids; D010743:Phospholipids; D003891:Desipramine