CYCLIC AMP-PHOSPHODIESTERASE-IIIA1 INHIBITORS DECREASE CYTOSOLIC CA2+CONCENTRATION AND INCREASE THE CA2+ CONTENT OF INTRACELLULAR STORAGE SITES IN HUMAN PLATELETS

The effect of cyclic AMP-phosphodiesterase (cAMP-PDE) inhibitors on Ca 2+ homeostasis in human platelets was studied using both quin-2 oxy)me thyl-6-methoxy-8-bis-(acetylamino)quinoline) and chlorotetracycline (C TC) to measure changes in cytosolic Ca2+ as well as changes in the amo unt of Ca2+ accumulated in intracellular storage sites. At therapeutic concentrations (1 muM) milrinone and R 80 122 but not enoximone decre ased the cytosolic Ca2+ concentration in the resting platelet while th e Ca2+ content in intracellular stores was increased. These observatio ns are in accord with the proposed mechanism of action of cAMP-PDE inh ibitors on cardiomyocites and highlight the particular role of cAMP in regulation of Ca2+ homeostasis.