Leukotriene D4 (LTD4) activates charybdotoxin-sensitive and -insensitive K+ channels in ehrlich ascites tumor cells.

Abstract

The putative role for ATP, UTP, bradykinin and leukotriene D4 (LTD4) in the activation of the charybdotoxin-insensitive, volume-activated K+ leak pathway has been assessed in Ehrlich cells. K+ channel activity is evaluated from bumetanide-insensitive 86Rb+ efflux using Rb+ as a tracer for K+. Addition of the Ca2+-mobilizing agonists bradykinin, ATP, UTP or LTD4 accelerates the regulatory volume decrease (RVD) response and activates a fast bumetanide-insensitive, charybdotoxin-sensitive efflux of K+. In addition LTD4 activates a charybdotoxin-insensitive K+ efflux, whereas bradykinin, ATP and UTP do not. The charybdotoxin-insensitive K+ efflux dominates after addition of LTD4 at concentrations too low to elicit an increase in [Ca2+]i but still high enough to be effective in accelerating the RVD response. The EC50 values for LTD4-induced K+ effluxes are estimated at 2 nM and 15 nM for the charybdotoxin-insensitive and charybdotoxin-sensitive components, respectively. The LTD4 (cysLT1) receptor antagonist L660,711(MK-571) blocks the activation of the charybdotoxin-sensitive but not the charybdotoxin-insensitive K+ efflux. Thus, LTD4 activates two different K+ leak pathways in Ehrlich cells, one pathway activated by an increase in [Ca2+]i and the other via an alternative signalling pathway. LTD4 is thus a potential candidate for an autocrine messenger activating the Ca2+-independent, charybdotoxin-insensitive K+ channel during the RVD response in Ehrlich cells.

• Authors: E K Hoffmann
• Journal: Pflugers Archiv : European journal of physiology (Pflugers Arch) Vol. 438 Issue 3 Pg. 263-8 (Aug 1999) ISSN: 0031-6768 [Print] Germany
• PMID: 10398854 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Leukotriene Antagonists
• Membrane Proteins
• Potassium Channels
• Propionates
• Quinolines
• Receptors, Leukotriene
• Rubidium Radioisotopes
• Bumetanide
• Charybdotoxin
• verlukast
• Leukotriene D4
• Adenosine Triphosphate
• cysteinyl leukotriene receptor 2
• leukotriene D4 receptor
• Potassium
• Bradykinin
• Calcium
• Uridine Triphosphate

Topics

• Adenosine Triphosphate (pharmacology)
• Animals
• Bradykinin (pharmacology)
• Bumetanide (pharmacology)
• Calcium (metabolism)
• Carcinoma, Ehrlich Tumor
• Charybdotoxin (pharmacology)
• Female
• Kinetics
• Leukotriene Antagonists (pharmacology)
• Leukotriene D4 (pharmacology)
• Membrane Proteins
• Mice
• Potassium (metabolism)
• Potassium Channels (drug effects, physiology)
• Propionates (pharmacology)
• Quinolines (pharmacology)
• Receptors, Leukotriene
• Rubidium Radioisotopes (metabolism)
• Uridine Triphosphate (pharmacology)