title: Cyclic nucleotide phosphodiesterase inhibitors prevent aggregation of human platelets by raising cyclic AMP and reducing cytoplasmic free calcium mobilization.
abstract: Cyclic nucleotide phosphodiesterase inhibitors (HL-725, RO 15-2041, cilostamide, quercetin and MY-5445) potently inhibit human platelet aggregation induced by ADP. In parallel, PDE inhibitors inhibit the increase in cytoplasmic free Ca2+ evoked by ADP, as measured with the fluorescent probe quin 2. The inhibition of ADP-induced aggregation and rise in [Ca2+]i is potentiated by PGE1 which stimulates adenylate cyclase and is inhibited by adrenaline which inhibits adenylate cyclase. PDE inhibitors increase human platelet cAMP levels in the presence of low concentrations of PGE1. It is suggested that PDE inhibitors prevent platelet aggregation by raising cAMP levels and by subsequent inhibition of cytoplasmic free Ca2+ mobilization.
mesh_terms: D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases / Q000037:antagonists & inhibitors*; D000527:Alprostadil / Q000494:pharmacology; D000634:Aminoquinolines / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects* / Q000201:enzymology; D002118:Calcium / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology; D010793:Phthalazines / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects*; D011794:Quercetin / Q000494:pharmacology; D011799:Quinazolines / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology; D015363:Quinolones; D044005:Tetrahydroisoquinolines
chemical_list: D000634:Aminoquinolines; D007546:Isoquinolines; D010793:Phthalazines; D011799:Quinazolines; D011804:Quinolines; D015363:Quinolones; D044005:Tetrahydroisoquinolines; C021294:cilostamide; C035964:trequinsin; C046655:Ro 15-2041; D011794:Quercetin; D000242:Cyclic AMP; D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases; D000527:Alprostadil; C052490:MY 5445; C035739:Quin2; D002118:Calcium