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

Prostaglandin E1 (PGE1), amrinone and milrinone not only inhibit platelet aggregation, but also potentially induce disaggregation. We examined the disaggregatory effects of PGE1, amrinone and milrinone on platelet aggregation, and measured the platelet cyclic adenosine monophosphate (cAMP) levels using a standard radioimmunoassay. Platelet aggregation was induced by 10 microM adenosine diphosphate (ADP) or 0.625 microg/ml collagen that induces a secondary aggregation, and measured by whole blood aggregometry. PGE1 (0.7-10.0 microM), amrinone (106.8-801.3 microM), or milrinone (9.5-190.0 microM) was added when aggregation reached 5 mohm of impedance, and the percentage of disaggregation was measured 5 min after initiating disaggregation. Disaggregatory effects were also examined using a light transmission aggregometer and gel-filtered platelets. In platelet aggregation induced by ADP, the drug concentrations required to cause 50% disaggregation (EC50) were PGE1; 3.1+/-1.2 microM, amrinone; 313.1+/-128.8 microM, milrinone; 57.1+/-20.8 microM. In platelet aggregation induced by collagen, the maximum disaggregation percentages were 15.6+/-5.0% for 10 microM PGE1, 7.8+/-2.4% for 801.3 microM amrinone, and 5.9+/-2.3% for 190.0 microM milrinone. The EC50 concentrations of platelet cAMP that caused 50% disaggregation in ADP-induced platelet aggregation were 67+/-13 pmoles/10(8) platelets for PGE1, 54+/-12 pmoles/10(8) platelets for amrinone, and 52+/-12 pmoles/10(8) platelets for milrinone. In gel-filtered platelets, the percentages of disaggregation in ADP- or collagen-induced platelet aggregation were 33.1+/-5.2% or 11.2+/-3.1% for PGE1 (10 microM), 22.3+/-4.1% or 15.2+/-3.2% for amrinone (801.3 microM), and 23.5+/-4.3% or 14.6+/-3.5% for milrinone (190.0 microM).