title: Role of LTD4 in the regulatory volume decrease response in Ehrlich ascites tumor cells.
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 microM) 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.
authors.affiliation: The August Krogh Institute, Biochemical Department, Universitetsparken 13, DK-2100 Copenhagen O, Denmark.
authors.forename: N K
authors.initials: NK
authors.lastname: Jorgensen
authors.forename: I H
authors.initials: IH
authors.lastname: Lambert
authors.forename: E K
authors.initials: EK
authors.lastname: Hoffmann
mesh_terms: D000818:Animals; D002021:Buffers; D002118:Calcium / Q000378:metabolism; D002147:Calmodulin / Q000037:antagonists & inhibitors; D002286:Carcinoma, Ehrlich Tumor / Q000473:pathology*; D048429:Cell Size / Q000187:drug effects; D002614:Chelating Agents / Q000494:pharmacology; D018118:Chloride Channels / Q000187:drug effects; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D007038:Hypotonic Solutions / Q000494:pharmacology; D007424:Intracellular Fluid / Q000378:metabolism; D015640:Ion Channel Gating / Q000187:drug effects; D020024:Leukotriene Antagonists; D017998:Leukotriene D4 / Q000494:pharmacology / Q000502:physiology*; D008565:Membrane Proteins; D051379:Mice; D009997:Osmotic Pressure; D010654:Phenylbutyrates / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects; D011189:Potassium Chloride / Q000378:metabolism; D018077:Receptors, Leukotriene / Q000187:drug effects / Q000502:physiology*; D014407:Tumor Cells, Cultured / Q000187:drug effects
chemical_list: D002021:Buffers; D002147:Calmodulin; D002614:Chelating Agents; D018118:Chloride Channels; D007038:Hypotonic Solutions; D020024:Leukotriene Antagonists; D008565:Membrane Proteins; D010654:Phenylbutyrates; D015221:Potassium Channels; D018077:Receptors, Leukotriene; D004533:Egtazic Acid; D011189:Potassium Chloride; D017998:Leukotriene D4; C050033:L 649923; C412375:cysteinyl leukotriene receptor 2; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; C083169:leukotriene D4 receptor; D002118:Calcium