Effect of heparin on platelet aggregation inhibited by PGI2, trifluoperazine and verapamil.
The enhancement of platelet aggregation by heparin in the presence of certain inhibitors of aggregation was investigated in an attempt to discern the mechanism through which heparin alters platelet function in plasma. These studies were performed by adding prostaglandin I2 (PGI2), verapamil, or trifluoperazine to platelet-rich plasma (PRP) in the presence or absence of heparin. Adenosine diphosphate (ADP), collagen, or arachidonic acid were used for induction of platelet aggregation. The inhibitory agents reduced platelet aggregation to 5 to 20% of control in the absence of heparin. When present in the reaction mixture along with the inhibitor, heparin restored aggregation to approximately 57 to 92% of control depending on the inhibitor and aggregating agent. This proaggregatory action of heparin was observed when heparin and PGI2 were preincubated together or separately for 20 min prior to the addition of PRP and ADP. Results were similar regardless of the sequence in which PGI2 and heparin were added to PRP, and irrespective of the time of incubation of platelets with PGI2. No suppression of platelet cyclic AMP concentration was observed with heparin alone. Heparin also failed to reduce the magnitude of platelet cyclic AMP accumulation promoted by PGI2, forskolin, or a mixture of PGI2 and forskolin. These observations suggest that heparin promoted platelet aggregation and partially overcame the effect of certain inhibitory agents by mechanism(s) that did not involve a reduction of platelet cyclic AMP.
D001792:Blood Platelets; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000097:blood; D003864:Depression, Chemical; D004347:Drug Interactions; D011464:Epoprostenol / Q000494:pharmacology*; D006493:Heparin / Q000494:pharmacology*; D006801:Humans; D010974:Platelet Aggregation / Q000187:drug effects*; D012701:Serotonin / Q000378:metabolism; D014268:Trifluoperazine / Q000494:pharmacology*; D014700:Verapamil / Q000494:pharmacology*
D005576:Colforsin; D014268:Trifluoperazine; D012701:Serotonin; D006493:Heparin; D014700:Verapamil; D011464:Epoprostenol; D000242:Cyclic AMP