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Role of LTD4 in the regulatory volume decrease response in Ehrlich ascites tumor cells

N K Jorgensen1, I H Lambert, E K Hoffmann

  • 1The August Krogh Institute, Biochemical Department, Universitetsparken 13, DK-2100 Copenhagen O, Denmark.

The Journal of Membrane Biology
|May 1, 1996
PubMed
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Leukotriene D4 (LTD4) activates cell volume regulation by opening ion channels, independent of significant calcium increases. This process involves LTD4 receptors and impacts cell shrinkage during regulatory volume decrease (RVD).

Area of Science:

  • Cellular Physiology
  • Ion Channel Function
  • Receptor Signaling

Background:

  • Leukotriene D4 (LTD4) is implicated in cellular responses.
  • Regulatory Volume Decrease (RVD) is a critical cellular process for maintaining cell volume.
  • The role of intracellular calcium in LTD4-mediated RVD is not fully understood.

Purpose of the Study:

  • To investigate the role of leukotriene D4 (LTD4) in regulating cell volume.
  • To determine the involvement of intracellular calcium ([Ca2+]i) in LTD4-induced RVD.
  • To elucidate the mechanism of LTD4 action on ion channels during RVD.

Main Methods:

  • Stimulation of Ehrlich ascites tumor cells with LTD4 in varying calcium concentrations.
  • Measurement of intracellular calcium ([Ca2+]i) using calcium-free medium and BAPTA buffering.

Related Experiment Videos

  • Assessment of KCl loss and cell shrinkage during Regulatory Volume Decrease (RVD).
  • Utilized LTD4 receptor antagonist (L649,923) and receptor desensitization.

    • Main Results:

    • LTD4 (3-100 nM) transiently increased intracellular calcium ([Ca2+]i) in Ehrlich ascites tumor cells.
    • LTD4 accelerated KCl loss during RVD, even in calcium-free conditions, indicating calcium-independent channel opening.
    • Buffering intracellular calcium with BAPTA significantly inhibited LTD4-accelerated RVD.
    • LTD4 receptor antagonism and desensitization blocked LTD4-induced effects on [Ca2+]i and RVD.

    Conclusions:

    • LTD4 plays a significant role in activating the Regulatory Volume Decrease (RVD) response.
    • LTD4 activates potassium (K+) and chloride (Cl-) channels via LTD4 receptor stimulation, without requiring a detectable increase in intracellular calcium.
    • Intracellular calcium levels modulate the LTD4-induced acceleration of RVD.