Effects of trifluoperazine, a calmodulin antagonist, on rabbit T- and B-cell responses to mitogens and antigen.
Trifluoperazine (TFP), an inhibitor of the calcium-binding protein, calmodulin (CaM), was used to assess the role of calmodulin in the responses of rabbit lymphoid cells to stimulation with mitogen and antigen. After binding goat anti-rabbit Fab antibody, rabbit B cells lose their surface immunoglobulin (Ig) through endocytosis and then reexpress this protein during the next 24 hr. This reexpression was markedly inhibited by TFP. The brief and early addition of TFP markedly inhibited the increased [3H]thymidine (Tdr) uptake by rabbit T cells treated with concanavalin A and B cells exposed to anti-Fab. TFP greatly inhibited the induction by keyhole limpet hemocyanin (KLH) of the in vitro syntheses of antibody, Ig, and protein by KLH-primed lymph node cells (LNC). The earlier the TFP the greater was the inhibition of induction of these syntheses. However, once induced, synthesis and secretion of antibody were not inhibited by TFP. In striking contrast to the inhibition by TFP of the mitogenic and antigenic responses of lymphoid cells was the lack of effect of this drug on resting lymphocytes. Since TFP was not cytotoxic for either resting or mitogen- or antigen-stimulated LNC, it is highly unlikely that the observed inhibitory effects of this drug were due to its cytotoxicity. We postulate that an early signal for the activation of LNC proliferation, differentiation, and the syntheses of antibody, Ig, and protein involves a calcium-CaM-mediated reaction. Based on this work and that of others, the calcium-CaM complex may mediate an interaction between the ligand-occupied surface receptor and the cytoskeleton.
D000818:Animals; D000917:Antibody Formation / Q000187:drug effects*; D000941:Antigens; D001402:B-Lymphocytes / Q000187:drug effects*; D002118:Calcium / Q000502:physiology; D002147:Calmodulin / Q000037:antagonists & inhibitors*; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D007152:Immunologic Capping / Q000187:drug effects; D008213:Lymphocyte Activation / Q000187:drug effects*; D008934:Mitogens; D011817:Rabbits; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects*; D014268:Trifluoperazine / Q000494:pharmacology*
D000941:Antigens; D002147:Calmodulin; D007140:Immunoglobulin Fab Fragments; D008934:Mitogens; D011947:Receptors, Antigen, B-Cell; D014268:Trifluoperazine; D002118:Calcium