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Cyclic AMP-phosphodiesterase IIIA1 inhibitors decrease cytosolic Ca2+ concentration and increase the Ca2+ content of
P Roevens1, D de Chaffoy de Courcelles
1Department of Biochemistry II, Janssen Research Foundation, Beerse, Belgium.
Abstract:
The effect of cyclic AMP-phosphodiesterase (cAMP-PDE) inhibitors on Ca2+ homeostasis in human platelets was studied using both quin-2 (2-(bis-(acetylamino)-5-methyl-phenoxy)methyl-6-methoxy-8-bis-(acetylami no) quinoline) and chlorotetracycline (CTC) to measure changes in cytosolic Ca2+ as well as changes in the amount of Ca2+ accumulated in intracellular storage sites. At therapeutic concentrations (1 microM) milrinone and R 80 122 but not enoximone decreased the cytosolic Ca2+ concentration in the resting platelet while the Ca2+ content in intracellular stores was increased. These observations are in accord with the proposed mechanism of action of cAMP-PDE inhibitors on cardiomyocites and highlight the particular role of cAMP in regulation of Ca2+ homeostasis.