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

Abstract

Prostaglandin E 1 (PGE 1 ), amrinone and milrinone not only inhibit platelet aggregation, but also potentially induce disaggregation. We examined the disaggregatory effects of PGE 1 , 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 w M adenosine diphosphate (ADP) or 0.625 w g/ml collagen that induces a secondary aggregation, and measured by whole blood aggregometry. PGE 1 (0.7-10.0 w M), amrinone (106.8-801.3 w M), or milrinone (9.5-190.0 w M) was added when aggregation reached 5 m z 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 (EC 50 ) were PGE 1 ; 3.1 - 1.2 w M, amrinone; 313.1 - 128.8 w M, milrinone; 57.1 - 20.8 w M. In platelet aggregation induced by collagen, the maximum disaggregation percentages were 15.6 - 5.0% for 10 w M PGE 1 , 7.8 - 2.4% for 801.3 w M amrinone, and 5.9 - 2.3% for 190.0 w M milrinone. The EC 50 concentrations of platelet cAMP that caused 50% disaggregation in ADP-induced platelet aggregation were 67 - 13 pmoles/10 8 platelets for PGE 1 , 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 PGE 1 (10 w M), 22.3 - 4.1% or 15.2 - 3.2% for amrinone (801.3 w M), and 23.5 - 4.3% or 14.6 - 3.5% for milrinone (190.0 w M).