TMB-8 inhibits secretion evoked by phorbol ester at basal cytoplasmic free calcium in quin2-loaded platelets much more effectively than it inhibits thrombin-induced calcium mobilisation

Abstract

TMB-8 is widely regarded as an ‘intracellular calcium antagonist’, supposedly inhibiting the mobilisation of intracellular calcium. Rarely, however, have the effects of this compound on Ca²⁺ movements been measured. We report here that TMB-8 is not very effective in inhibiting thrombin-induced Ca²⁺ influx or internal release in human platelets judged from the fluorescent signal of cytoplasmic quin2. Only approx. 40% inhibition was seen at 500 μm TMB-8. Somewhat lower concentrations blocked the secretory response to thrombin and also the secretion evoked at basal [Ca²⁺]_i by phorbol ester and collagen. It is suggested that one target for TMB-8 may be the C-kinase pathway.