The response of platelets to epinephrine in storage pool deficiency--evidence pertaining to the role of adenosine diphosphate in mediating primary and secondary aggregation.
Aggregation responses and thromboxane (Tx) formation in ten patients with storage pool deficiency (SPD) specific to the dense granules (delta-SPD) were studied to assess further the role of dense granule adenosine diphosphate (ADP) in mediating platelet aggregation by epinephrine. The ability of epinephrine to elicit secondary aggregation (SA) responses was highly variable in delta-SPD when tested at 5 mumol/L epinephrine, but was consistently abnormal when tested over a range of concentrations. The occurrence of SA in both delta-SPD patients and normal subjects was correlated with the magnitude of the rate of primary aggregation (PA). This PA rate was normal, on average, for the entire patient group but was greater in patients with more consistent SA responses. The PA findings were related to the Kd value obtained in binding studies with 3H-yohimbine, but not with the number of alpha 2-receptor sites. Studies on Tx production (assessed by radioimmunoassay of TxB2) showed that the ability to synthesize Tx from arachidonate was not impaired in delta-SPD, and that there was an absolute positive correlation between epinephrine-induced SA and Tx production. Aggregation in delta-SPD platelets in response to the Tx receptor agonist U44069 was consistently decreased, but could be corrected by addition of ADP. The results of the study suggest that dense granule-derived ADP is not required for PA by epinephrine, but mediates SA as a synergistic agonist with TxA2. This role of ADP in SA may be elucidated more precisely by further studies on platelet activation processes in delta-SPD.
Weiss
H J
HJ
Department of Medicine (Division of Hematology-Oncology), St. Luke's-Roosevelt Hospital Center, New York, NY 10019.
Lages
B
B
D000244:Adenosine Diphosphate / Q000097:blood / Q000494:pharmacology*; D001791:Blood Platelet Disorders / Q000097:blood*; D001792:Blood Platelets / Q000502:physiology* / Q000648:ultrastructure; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D010974:Platelet Aggregation / Q000187:drug effects*; D010981:Platelet Storage Pool Deficiency / Q000097:blood*; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism; D013929:Thromboxane B2 / Q000096:biosynthesis; D015016:Yohimbine / Q000378:metabolism
D011450:Prostaglandin Endoperoxides, Synthetic; D011942:Receptors, Adrenergic, alpha; D015016:Yohimbine; D013929:Thromboxane B2; D000244:Adenosine Diphosphate; D004837:Epinephrine