Effects of the lonophore A23187 on blood platelets I. Influence on aggregation and secretion

A23187 is an antibiotic ionophore which transports divalent cations across cell membranes into the cytoplasm and releases cations from intracellular storage sites. The present investigation has studied the influence of A23187 on blood platelet aggregation and secretion. A23187 added to stirred C-PRP produced concentration-dependent aggregation and release of (14)C-serotonin. Calcium ions potentiated the response of platelets in washed suspensions to A23187, but they were not required for ionophore-induced aggregation or release. N-ethylmaleimide and agents which increase the level of cyclic 3',5'-adenosine monophosphate (cAMP) in platelets were effective inhibitors of A23187-induced aggregation and secretion.Platelets incubated with (45)Ca(++) before addition of A23187 increased their content of isotope by 50% within 45 seconds after exposure to the ionophore. The results indicate that an increase in the cytoplasmic concentration of calcium ions from intracellular sources may be the critical event in triggering platelet contraction and the release reaction. Increased concentrations of cAMP may inhibit the platelet response to A23187 and other aggregating agents by stimulating a calcium extrusion pump.