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.
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 microns 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.
D000634:Aminoquinolines; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000097:blood*; D002121:Calcium Channel Blockers; D003094:Collagen / Q000494:pharmacology; D005456:Fluorescent Dyes; D005707:Gallic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D010704:Phorbols / Q000494:pharmacology*; D010766:Phosphorylation; D011493:Protein Kinase C; D047428:Protein Kinase Inhibitors; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D013917:Thrombin / Q000494:pharmacology*
D000634:Aminoquinolines; D002121:Calcium Channel Blockers; D005456:Fluorescent Dyes; D010704:Phorbols; D047428:Protein Kinase Inhibitors; C006014:8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate; D005707:Gallic Acid; D003094:Collagen; D011493:Protein Kinase C; D013917:Thrombin; D013755:Tetradecanoylphorbol Acetate; C035739:Quin2; D002118:Calcium