Inhibition by staurosporine of mitogen-induced calcium mobilisation in human T lymphoblasts.
Addition of monoclonal antibodies (UCHT1) directed against the antigen receptor/CD3 complex or the addition of the mitogens concanavalin A or phytohemagglutinin to human T lymphoblasts induced an elevation of the cytosolic free calcium concentration [( Ca2+]i) as monitored by the fluorescence of the intracellular fura-2. The rise in [Ca2+]i induced by these agents was effectively inhibited by staurosporine, an agent which inhibits protein kinase (PK)C and PKA. Conversely the PKC activator 12-O-tetradecanoyl phorbol-13-acetate decreased the delay and accelerated the rate of elevation of [Ca2+]i induced by the mitogens and UCHT1. Increasing the concentration of cAMP or cGMP in the T lymphoblasts had no effect on agonist-induced elevation of [Ca2+]i. Our data indicate that PKC can exert a positive feedback on the level of cytosolic Ca2+ in T lymphocytes, in contrast to what has been observed with other cells.
Ward
S G
SG
Department of Pharmacology, Royal College of Surgeons, London, England.
Cantrell
D
D
Westwick
J
J
D000470:Alkaloids / Q000494:pharmacology*; D000911:Antibodies, Monoclonal; D002118:Calcium / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008213:Lymphocyte Activation; D008934:Mitogens / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D019311:Staurosporine; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000470:Alkaloids; D000911:Antibodies, Monoclonal; D008934:Mitogens; D011948:Receptors, Antigen, T-Cell; D011493:Protein Kinase C; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium