XXXX -induced inhibition of proliferation of @entity1 peripheral blood mononuclear cells.

@entity1 @entity1199 @entity946 @entity37239 @entity665 @entity460 @entity594 @entity141 @entity9898
To evaluate the role of intracellular @entity460 and particularly @entity141 -uptake in the initiation of lymphocyte mitogenesis, the effect of @entity946 , which blocks both L- and T-type @entity460 channels with a more selective blockade of T-type channels, on the proliferation of @entity1 peripheral blood mononuclear cells (PBMCs) is compared with the effect of @entity594 , which blocks only the L-type @entity460 channel. The rate of @entity665 incorporation into control and concanavalin A-stimulated PBMCs in the presence or absence of the @entity460 channel blockers @entity946 or @entity594 (1, 10, or 50 microM), and of the intracellular @entity460 antagonist @entity37239 ( @entity37239 ; 1, 10, 25, or 50 microM) was assayed in the cells cultured for 3 days. The cellular cytotoxicity and the cell number in growing cultures also was determined in @entity946 - or @entity594 -treated control or stimulated cells. Restoration of the proliferative response in @entity946 - or @entity594 -treated cells was investigated by addition of exogenous @entity1199 . @entity1199 -receptor expression in the cells was monitored by using anti-activated T-cell antigen (Tac) antibody, and the @entity1199 production in the cell supernatants of the cultures was determined by an enzyme-amplified sensitive immunoassay. @entity946 and @entity594 concentration-dependently reduced the cell number and the @entity665 incorporation or the de novo DNA synthesis in control and concanavalin A-stimulated @entity1 PBMCs. @entity946 exhibited a more pronounced inhibition of the proliferation of @entity1 PBMCs than did @entity594 . The inhibitory effect of @entity946 or @entity594 on DNA synthesis was dependent on the timing of treatment with the drugs. The inhibitory effect of @entity946 or @entity594 on the lymphoproliferative response was nearly abolished if the drugs were added 20 h after cell stimulation. A markedly reduced inhibitory effect was found when @entity946 or @entity594 was added 1-7 h after cell stimulation. However, regardless of time of addition, TMB-8 caused a persistent inhibition of the proliferation of @entity1 PBMCs. The inhibitory effect of @entity946 or @entity594 on the proliferation of @entity1 PBMCs is nearly abolished by addition of the @entity460 channel activator @entity9898 . The proliferative response of @entity946 - or @entity594 -treated cells is restored by addition of exogenous @entity1199 . The normal expression of @entity1199 receptors was preserved, whereas the @entity1199 production was blocked in the presence of @entity946 or @entity594 . Our data show that @entity946 has a more pronounced inhibitory effect on the proliferation of @entity1 PBMCs than @entity594 and that this inhibitory effect on DNA synthesis is dependent on the timing of treatment with both drugs.
