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 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.
Roevens
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Department of Biochemistry II, Janssen Research Foundation, Beerse, Belgium.
de Chaffoy de Courcelles
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D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D000634:Aminoquinolines; D001792:Blood Platelets / Q000187:drug effects* / Q000201:enzymology; D002118:Calcium / Q000378:metabolism*; D002751:Chlortetracycline; D003600:Cytosol / Q000187:drug effects; D017335:Enoximone / Q000494:pharmacology; D006321:Heart / Q000187:drug effects; D006706:Homeostasis; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D020105:Milrinone; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D011728:Pyridones / Q000494:pharmacology; D011799:Quinazolines / Q000494:pharmacology
D000634:Aminoquinolines; D007093:Imidazoles; D010726:Phosphodiesterase Inhibitors; D011728:Pyridones; D011799:Quinazolines; C076518:R 80122; D017335:Enoximone; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D020105:Milrinone; C035739:Quin2; D002118:Calcium; D002751:Chlortetracycline