Abstract.
Stimulation with leukotriene D4 (LTD4) (3–100 nm) induces a transient increase in the free intracellular Ca2+ concentration ([Ca2+] i ) in Ehrlich ascites tumor cells. The LTD4-induced increase in [Ca2+] i is, however, significantly reduced in Ca2+-free medium (2 mm EGTA), and under these conditions stimulation with a low LTD4 concentration (3 nm) does not result in any detectable increase in [Ca2+] i . Addition of LTD4 (3–100 nm) moreover accelerates the KCl loss seen during Regulatory Volume Decrease (RVD) in cells suspended in a hypotonic medium. The LTD4-induced (100 nm) acceleration of the RVD response is also seen in Ca2+-free medium and also at 3 nm LTD4, indicating that LTD4 can open K+- and Cl−-channels without any detectable increase in [Ca2+] i . Buffering cellular Ca2+ with BAPTA almost completely blocks the LTD4-induced (100 nm) acceleration of the RVD response. Thus, the reduced [Ca2+] i level after BAPTA-loading or buffering of [Ca2+] i seems to inhibit the LTD4-induced stimulation of the RVD response even though the LTD4-induced cell shrinkage is not necessarily preceded by any detectable increase in [Ca2+] i . The LTD4 receptor antagonist L649,923 (1 μm) completely blocks the LTD4-induced increase in [Ca2+] i and inhibits the RVD response as well as the LTD4-induced acceleration of the RVD response. When the LTD4 receptor is desensitized by preincubation with 100 nm LTD4, a subsequent RVD response is strongly inhibited. In conclusion, the present study supports the notion that LTD4 plays a role in the activation of the RVD response. LTD4 seems to activate K+ and Cl− channels via stimulation of a LTD4 receptor with no need for a detectable increase in [Ca2+] i .
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Received: 25 September 1995/Revised: 25 January 1996
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Jørgensen, N., Lambert, I. & Hoffmann, E. Role of LTD4 in the Regulatory Volume Decrease Response in Ehrlich Ascites Tumor Cells. J. Membrane Biol. 151, 159–173 (1996). https://doi.org/10.1007/s002329900067
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DOI: https://doi.org/10.1007/s002329900067