Elsevier

Biochemical Pharmacology

Volume 39, Issue 9, 1 May 1990, Pages 1437-1443
Biochemical Pharmacology

Single and multiple desipramine exposures of cultured cells: Changes in cellular anisotropy and in lipid composition of whole cells and of plasma membranes

https://doi.org/10.1016/0006-2952(90)90425-KGet rights and content

Abstract

Effects of the antidepressant drug desipramine (DMI) on fluorescence anisotropy were studied in living cultured human fibroblasts, rat brain astrocytes and rat ROC-1 hybridoma cells (oligodendrocytes × C6). Fluorescence anisotropy, a measure for fluidity, was measured by means of a fluorescence polarization technique using a set of n-(9-anthroyloxy) fatty acids as markers. Apparent fluorescence anisotropies were determined in cells following single or multiple dose exposures to 5 μm DMI at 37° and compared to control cells. In all three cell types single doses of DMI led to significant decreases in anisotropies of the deeper layers (12-AS) of the membranes only, suggesting increases in fluidity. Repeated exposures to 5 μM DMI led to cell specific, significant changes in anisotropies of the superficial membrane layers, as determined by 2-AP, 6-, 7- and 9-AS. The resulting anisotropy values of the three different cell types became more alike than prior to DMI exposure. Alterations in anisotropies were accompanied with changes in the phospholipid patterns of whole cells and isolated plasma membrane vesicles. The changes of PC/PE ratios were consistent with changes observed in fluorescence anisotropies. Such alterations may be individual regulatory responses of the cells to the chronic presence of the drug within the membranes.

References (28)

  • B Kursch et al.

    Influence of various cationic amphiphilic drugs on the phase transition temperature of phosphatidylcholine liposomes

    Biochem Pharmacol

    (1983)
  • H Lüllmann et al.

    Drug-induced phospholipidosis

    Germ Med

    (1973)
  • KY Hosteller et al.

    Studies on the mechanism of phospholipid storage induced by amantadine and chloroquine in madin darby canine kidney cells

    Biochem Pharmacol

    (1982)
  • DS Heron et al.

    Lipid fluidity markedly modulates the binding of serotonin to mouse brain membranes

  • Cited by (26)

    • St John's wort extract influences membrane fluidity and composition of phosphatidylcholine and phosphatidylethanolamine in rat C6 glioblastoma cells

      2019, Phytomedicine
      Citation Excerpt :

      Chronic incubation of C6 cells with the antidepressants DMI and citalopram revealed no changes of the PC/PE ratio within whole cell lipid extracts, as suggested by the absence of a change in TMA-DPH fluorescence anisotropy. Interestingly, in rat ROC-1 cells exposed for several days to a high concentration of DMI a decrease in the PC/PE ratio was demonstrated, while human fibroblasts under identical conditions showed the opposite effect (Toplak et al., 1990). Another similar in vivo study also determined a non-significant change of the PC/PE ratio in brain homogenates, following daily i.p. injections (21 days) of DMI to rats (Moor et al., 1988).

    • Chemical genetic screening identifies tricyclic compounds that decrease cellular melanin content

      2008, Journal of Investigative Dermatology
      Citation Excerpt :

      For example, imipramine induces lysosomal accumulation of cholesterol by blocking the postlysosomal transport of cholesterol (Roff et al., 1991; Palmeri et al., 1992; Sato et al., 1998). Honegger et al. have reported that chronic desipramine exposure results in alteration of the cellular and membranous phospholipid patterns (Toplak et al., 1990) and promotes lysosomal phospholipid accumulation (Honegger et al., 1983). The same group later reported that chronic exposure to desipramine also impairs β1-adrenoceptor recycling in rat C6 glioblastoma cells through a modulation of receptor trafficking pathways (Bürgi et al., 2003).

    • Antidepressant-induced switch of β<inf>1</inf>-adrenoceptor trafficking as a mechanism for drug action

      2003, Journal of Biological Chemistry
      Citation Excerpt :

      As shown for mannose 6-phosphate receptors by Gonzalez-Noriega et al. (56), definitive fate decisions may be made as late as 3–4 h after internalization, because receptors could still be salvaged within this time period, whereas intervention at later time points could not prevent degradation in the lysosomal compartment anymore. We previously reported that chronic DMI exposure results in alterations of the cellular and membranous phospholipid patterns (11) and promotes lysosomal phospholipid accumulation (57). The modification of the physicochemical membrane characteristics does not interfere with receptor binding and internalization.

    View all citing articles on Scopus
    View full text