Suppression of lymphocyte mitogenesis by tamoxifen: Studies on protein kinase C, calmodulin and calcium

The effect of tamoxifen (TX; 1.0 mu M) on the mitogenic response of rat lym phocytes was compared with the effect of drugs that are known to act on pro tein kinase C (PKC), calmodulin (CM), and calcium (Ca2+). The calcium ionop hore A23187 (0.2 mu M) was mitogenic on its own which was not influenced by TX, The agents modulating PKC or CM (phorbol-myristate-13-acetate; R24571, chlorpromazine) influenced mitogenesis differently than did TX, General in hibition of lymphocyte proliferation was seen with the Ca2+ antagonist agen ts (EGTA, TMB-8) as with TX. The antiproliferative effect of TX was partial ly reversed by the increase of Ca2+ in the culture medium when T cell mitog ens were used, but not in the case of lipid A, a B lymphocyte mitogen. Howe ver, the concanavalin A-induced Ca2+ influx was further elevated by TX whic h differed from the effect of the Ca2+ channel-blocking agent verapamil. Th e results suggest that TX resets the threshold stimulus necessary for mitog enesis and is completely reversible. Copyright (C) 2000 S. Karger AG, Basel .