Leukotriene B4 mobilizes calcium without the breakdown of polyphosphoinositides and the production of phosphatidic acid in rabbit neutrophils.
The addition of fMet-Leu-Phe, leukotriene B4, or arachidonic acid to rabbit neutrophils causes a rise in the level of intracellular free calcium as measured by the fluorescent dye quin-2. The calcium response is rapid and dose-dependent with an ED50 of 0.12 +/- 0.05 nM for leukotriene B4, 0.20 +/- 0.02 nM for fMet-Leu-Phe, and 320 +/- 30 nM for arachidonic acid. However, unlike fMet-Leu-Phe, leukotriene B4 at concentrations up to 70 nM does not cause a significant breakdown of any of the phosphoinositides or the generation of phosphatidic acid, arachidonic acid, or 1,2-diacylglycerol. The addition of arachidonic acid causes little (less than 20%) production of phosphatidic acid. Furthermore, the dose-response curve of the generation of phosphatidic acid by fMet-Leu-Phe is shifted to the right when compared with that for calcium mobilization. The results reported here indicate that, although similar in many respects, there are important qualitative differences between the mechanisms of action of these two chemotactic factors. They also show that calcium mobilization by leukotriene B4 is not mediated by the breakdown of any of the phosphoinositides, and calcium mobilization by leukotriene B4, arachidonic acid, and possibly fMet-Leu-Phe is not mediated by the generation of phosphatidic acid.
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000097:blood; D002118:Calcium / Q000097:blood*; D004075:Diglycerides / Q000097:blood; D007700:Kinetics; D007975:Leukotriene B4 / Q000494:pharmacology*; D009504:Neutrophils / Q000378:metabolism*; D010712:Phosphatidic Acids / Q000097:blood*; D018129:Phosphatidylinositol Phosphates; D010716:Phosphatidylinositols / Q000097:blood*; D010761:Phosphorus Radioisotopes; D011817:Rabbits
D001095:Arachidonic Acids; D004075:Diglycerides; D010712:Phosphatidic Acids; D018129:Phosphatidylinositol Phosphates; D010716:Phosphatidylinositols; D010761:Phosphorus Radioisotopes; D007975:Leukotriene B4; D016718:Arachidonic Acid; D002118:Calcium