Conditions affecting the responses of human platelets to epinephrine.
Conditions affecting the responses of human platelets to epinephrine were examined. In platelet-rich plasma prepared from blood anticoagulated with hirudin or PPACK (D-phenylalanyl-L-prolyl-L-arginine chloromethyl ketone), epinephrine did not cause shape change or aggregation. In a Tyrode-albumin-apyrase solution containing a concentration of Ca2+ in the physiological range, and fibrinogen, epinephrine in concentrations as high as 40 microM did not induce platelet shape change, caused either no primary aggregation or very slight primary aggregation, and did not induce thromboxane formation, release of dense granule contents, or secondary aggregation. In contrast, in citrated platelet-rich plasma, epinephrine induced two phases of aggregation. This is not attributable to the generation of traces of thrombin since the same effects were evident when blood was taken into a combined citrate-hirudin anticoagulant or a combined citrate-PPACK anticoagulant. In a modified Tyrode-albumin-apyrase solution containing approximately 20 microM Ca2+, 1 mM Mg2+, and fibrinogen, epinephrine induced extensive aggregation after a lag phase, but no primary phase was evident; thromboxane formation and release of dense granule contents accompanied the aggregation response. These responses were also observed when PPACK was included with the acid-citrate-dextrose anticoagulant, and in the washing and resuspending fluids. In the presence of aspirin or the thromboxane receptor blocker BM 13,177 a few small aggregates were detected by particle counting and by scanning electron microscopy; with the latter inhibitor, the platelets in the aggregates retained their disc shape; secondary aggregation and the responses associated with it did not occur.(ABSTRACT TRUNCATED AT 250 WORDS)
Lalau Keraly
C
C
Dept. of Pathology, McMaster University, Hamilton, Ontario, Canada.
Kinlough-Rathbone
R L
RL
Packham
M A
MA
Suzuki
H
H
Mustard
J F
JF
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000991:Antithrombins / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects* / Q000648:ultrastructure; D002118:Calcium / Q000494:pharmacology; D004357:Drug Synergism; D004837:Epinephrine / Q000494:pharmacology*; D006629:Hirudins / Q000494:pharmacology; D006801:Humans; D008855:Microscopy, Electron, Scanning; D010974:Platelet Aggregation / Q000187:drug effects
D000590:Amino Acid Chloromethyl Ketones; D000991:Antithrombins; D006629:Hirudins; D000244:Adenosine Diphosphate; C040308:phenylalanyl-prolyl-arginine-chloromethyl ketone; D002118:Calcium; D004837:Epinephrine