Disaggregatory effects of prostaglandin E-1, amrinone and milrinone on platelet aggregation in human whole blood

Prostaglandin E-1 (PGE(1)), amrinone and milrinone not only inhibit platele t aggregation, but also potentially induce disaggregation. We examined the disaggregatory effects of PGE(1), amrinone and milrinone on platelet aggreg ation, and measured the platelet cyclic adenosine monophosphate (cAMP) leve ls using a standard radioimmunoassay. Platelet aggregation was induced by 1 0 muM adenosine diphosphate (ADP) or 0.625 mug/ml collagen that induces a s econdary aggregation, and measured by whole blood aggregometry. PGE(1) (0.7 -10.0 muM), amrinone (106.8-801.3 muM), or milrinone (9.5-190.0 muM) was ad ded when aggregation reached 5 m Omega of impedance, and the percentage of disaggregation was measured 5 min after initiating disaggregation. Disaggre gatory effects were also examined using a light transmission aggregometer a nd gel-filtered platelets. In platelet aggregation induced by ADP, the drug concentrations required to cause 50% disaggregation (EC50) were PGE(1); 3. 1 +/- 1.2 muM, amrinone; 313.1 +/- 128.8 muM, milrinone; 57.1 +/- 20.8 muM. In platelet aggregation induced by collagen, the maximum disaggregation pe rcentages were 15.6 +/- 5.0% for 10 muM PGE(1), 7.8 +/- 2.4% for 801.3 muM amrinone, and 5.9 +/- 2.3% for 190.0 muM milrinone. The EC50 concentrations of platelet cAMP that caused 50% disaggregation in ADP-induced platelet ag gregation were 67 +/- 13 pmoles/10(8) platelets for PGE(1), 54 +/- 12 pmole s/10(8) platelets for amrinone, and 52 +/- 12 pmoles/10(8) platelets for mi lrinone. In gel-filtered platelets, the percentages of disaggregation in AD P- or collagen-induced platelet aggregation were 33.1 +/- 5.2% or 11.2 +/- 3.1% for PGE(1) (10 muM), 22.3 +/- 4.1% or 15.2 +/- 3.2% for amrinone (801. 3 muM), and 23.5 +/- 4.3% or 14.6 +/- 3.5% for milrinone (190.0 muM).