Stimulation of the T3-T cell receptor-associated Ca2+ influx enhances the activity of the Na+/H+ exchanger in a leukemic human T cell line.
Three monoclonal antibodies reactive with different structural domains of the T3-T cell receptor complex of the human T cell leukemia line, HPB-ALL, were previously shown to activate a membrane potential-sensitive, La3+-inhibitable Ca2+ influx (Oettgen, H. C., Terhorst, C., Cantley, L. C., and Rosoff, P. M. (1985) Cell 40, 583-590). OKT3 (anti-T3), WT-31 (anti-receptor constant region), and T40/25 (anti-receptor variable region) also enhance the activity of the Na+/H+ exchanger in these cells. The associated rise in pHi was dependent on the presence of external Ca2+ and Na+, was inhibited by dimethylamiloride and La3+, and was maintained for at least 20 min. Phorbol esters, which are co-mitogenic in T cells and activate protein kinase C, also stimulated the exchanger, but by a mechanism not requiring an elevation in cytoplasmic Ca2+; the rise in pHi rapidly peaked and returned to baseline levels within 20 min. Pretreatment with phorbols prevented an increase in pHi by OKT3 although a transient additive effect was observed when the two were added simultaneously. Receptor function was maintained in the presence of phorbol esters as OKT3 still stimulated a Ca2+ influx. These data demonstrate the existence of two interdependent pathways to activate Na+/H+ exchange in T lymphocytes and suggest a pathway of internal regulation of antigen-activated signal transduction.
D000584:Amiloride / Q000031:analogs & derivatives / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000276:immunology; D000954:Antigens, Surface / Q000276:immunology; D002118:Calcium / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D002460:Cell Line; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007811:Lanthanum / Q000494:pharmacology; D007945:Leukemia, Lymphoid / Q000276:immunology*; D010703:Phorbol Esters / Q000494:pharmacology; D011971:Receptors, Immunologic / Q000502:physiology*; D017923:Sodium-Hydrogen Exchangers; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D002352:Carrier Proteins; D010703:Phorbol Esters; D011971:Receptors, Immunologic; D017923:Sodium-Hydrogen Exchangers; C039465:5-dimethylamiloride; D007811:Lanthanum; D000584:Amiloride; D002118:Calcium