The effects of N-(5-vinyl-1,3-thiazolidin-2-ylidene)phenylamine (5-VTPA) on the changes in free intracellular calcium and the production of reactive oxygen metabolites in human leukocytes.
Human leukocytes were exposed to N-(5-vinyl-1,3-thiazolidin-2-ylidene)phenylamine (5-VTPA), a postulated impurity in the case oils that caused the Spanish Toxic Oil Syndrome in 1981. Changes induced by 5-VTPA alone and together with a chemotactic peptide, formyl-methionyl-leucyl-phenylalanine (FMLP), a tumor promoter, phorbol myristate acetate (PMA), or a synthetic diacylglycerol, dioctanoyl-s,n-glycerol (DiC8) in free intracellular calcium levels ([Ca2+]i) and in the induction of oxidative burst were measured. 5-VTPA elevated dose-dependently [Ca2+]i and induced the production of reactive oxygen metabolites in leukocytes. 5-VTPA also amplified FMLP-induced increase in [Ca2+]i, but was without an effect on FMLP-induced oxidative burst. On the contrary, 5-VTPA amplified dose-dependently PMA- and DiC8-induced respiratory burst. The present results indicate that 5-VTPA may interfere with transmembrane signalling in human leukocytes. 5-VTPA may elevate [Ca2+]i by acting directly on the membrane, or by acting through Ca(2+)-mobilizing receptors. Moreover, 5-VTPA also clearly amplified responses produced through protein kinase C stimulation. Thus, 5-VTPA may act on human leukocytes by affecting Ca(2+)-metabolism and the activity of protein kinase C.
Heiskanen
K M
KM
National Public Health Institute, Department of Toxicology, Kuopio, Finland.
Naarala
J
J
Savolainen
K M
KM
D002118:Calcium / Q000378:metabolism*; D002462:Cell Membrane / Q000187:drug effects; D002499:Centrifugation, Density Gradient; D004075:Diglycerides / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006801:Humans; D007962:Leukocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008163:Luminescent Measurements; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000633:toxicity; D011493:Protein Kinase C / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D016897:Respiratory Burst / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity; D013844:Thiazoles / Q000633:toxicity*; D053778:Thiazolidines
D004075:Diglycerides; D017382:Reactive Oxygen Species; D013844:Thiazoles; D053778:Thiazolidines; C044295:1,2-dioctanoylglycerol; C060009:N-(5-vinyl-1,3-thiazolidin-2-ylidene)phenylamine; D009240:N-Formylmethionine Leucyl-Phenylalanine; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium