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

• Published in: FEBS letters 1984-10, Vol.176 (1), p.139-143
• Main Authors: Simpson, A.W.M., Hallam, T.J., Rink, T.J.
• Format: Article
• Language: English
• Subjects: Aminoquinolines; Biological and medical sciences; Blood coagulation. Blood cells; Blood Platelets - drug effects; Blood Platelets - metabolism; Calcium; Calcium - blood; Calcium Channel Blockers; Collagen - pharmacology; Fluorescent Dyes; Fundamental and applied biological sciences. Psychology; Gallic Acid - analogs & derivatives; Gallic Acid - pharmacology; Humans; Molecular and cellular biology; Phorbol ester; Phorbols - pharmacology; Phosphorylation; Platelet; Protein Kinase C; Protein Kinase Inhibitors; Secretion; Tetradecanoylphorbol Acetate - pharmacology; Thrombin - pharmacology; TMB-8
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/0014-5793(84)80928-X

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 Ca 2+ movements been measured. We report here that TMB-8 is not very effective in inhibiting thrombin-induced Ca 2+ 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 [Ca 2+] i by phorbol ester and collagen. It is suggested that one target for TMB-8 may be the C-kinase pathway.