A comparison of dimaprit, nordimaprit, methylamine and chloroquine as inhibitors of mitogen-induced lymphocyte activation.
Methylamine and chloroquine both 'lysosomotropic' agents (i.e. agents which sequester in lysosomes) caused a dose-related inhibition of mitogen-induced lymphocyte activation in the concentrations which have previously been shown to increase the pH of lysosomes. The dose-response curves of inhibition of mitogen-induced lymphocyte activation for chloroquine and methylamine are very steep and are similar to the dose-response curves obtained with dimaprit and nordimaprit, but very different from the flat dose-response curves previously described for histamine. Approximate IC50 values were methylamine 6.4 mM, dimaprit 0.13 mM, nordimaprit 0.03 mM and chloroquine 18 microM. It is suggested that the mechanism of action of methylamine and chloroquine may be related to their lysosomotropic action and consequent interference with ligand-receptor processing, and that dimaprit and nordimaprit but not histamine may act by a similar mechanism.
D002478:Cells, Cultured; D002738:Chloroquine / Q000494:pharmacology*; D002860:Chromium Radioisotopes; D003208:Concanavalin A / Q000037:antagonists & inhibitors; D017259:Dimaprit / Q000031:analogs & derivatives; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects*; D008214:Lymphocytes / Q000378:metabolism; D008744:Methylamines / Q000494:pharmacology*; D008934:Mitogens / Q000037:antagonists & inhibitors; D010835:Phytohemagglutinins / Q000037:antagonists & inhibitors; D013890:Thiourea / Q000031:analogs & derivatives* / Q000494:pharmacology*; D013936:Thymidine / Q000378:metabolism
D002860:Chromium Radioisotopes; D008744:Methylamines; D008934:Mitogens; D010835:Phytohemagglutinins; D003208:Concanavalin A; C025838:nordimaprit; D006632:Histamine; D002738:Chloroquine; C027451:methylamine; D013890:Thiourea; D013936:Thymidine; D017259:Dimaprit