Bretylium differentiates between distinct signal transducing pathways in human lymphocytes.
The selection of signal transducing pathways of T cells depends on the type of triggers. Antigens, antibodies or lectins induce the T cell receptor-CD3 operated pathway, and IL-2 transmits its activation signal via the IL-2 receptor. It has been demonstrated that bretylium, a quaternary ammonium ion, can significantly inhibit the first pathway at the same dose range that stimulates cell activation through the IL-2 receptor system. In the light of the different complexity of the two pathways at the plasma membrane level, and the non-toxic and reversible behavior of the drug, it is suggested that the bretylium induced sustained membrane hyperpolarization is responsible for the observation. This finding may open new possibilities in studying the mechanism of different signal transducing pathways.
Pieri
C
C
Department of Gerontology and Geriatrics, INRCA, Ancona, Italy.
Bacsó
Z
Z
Recchioni
R
R
Moroni
F
F
Balázs
M
M
Gáspár
R
R
Damjanovich
S
S
D015152:Blotting, Northern; D001949:Bretylium Compounds / Q000494:pharmacology*; D017252:CD3 Complex / Q000502:physiology; D002462:Cell Membrane / Q000502:physiology; D015870:Gene Expression; D016259:Genes, myc / Q000235:genetics; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D008214:Lymphocytes / Q000187:drug effects / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D015375:Receptors, Interleukin-2 / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects*
D001949:Bretylium Compounds; D017252:CD3 Complex; D007376:Interleukin-2; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; D015375:Receptors, Interleukin-2; C045166:bretylium