The effects of cytochalasins on lymphocytes: V. Interaction of trifluoperazine and cytochalasin B in inhibition of human lymphocyte proliferation.

Trifluoperazine (TFP), a phenothiazine derivative, is known to inhibit calmodulin-mediated phenomena. We report here that TFP reversibly inhibited lymphocyte proliferative responses to mitogenic lectins. This inhibition was observed only when TFP was added during the early stages of exposure of lymphocytes to the stimulus. Furthermore, at suboptimally inhibitory concentrations of each compound, effects of TFP on lymphocyte proliferation were additive to those of cytochalasin B (CB). Incubation of lymphocytes in TFP (10(-5)-10(-4) M) markedly inhibited cytochalasin B binding to the actin associated, low affinity binding site without affecting its binding to the high affinity site or to the medium affinity site. This effect developed gradually during incubation with TFP, becoming demonstrable after 30 minutes reaching maximum after 30-60 min of incubation at 37 degrees. The findings suggest the occurrence of an interaction of TFP with the lymphocyte cytoskeleton, which may play a role in the impairment in the transmission of the mitogenic signal.