Epinephrine potentiation of arachidonate-induced aggregation of cyclooxygenase-deficient platelets.
Evaluation of platelet physiology, biochemistry, ultrastructure, and function in a young woman without history of hemorrhagic problems revealed that her platelets were deficient in cyclooxygenase activity. Her citrate platelet-rich plasma (C-PRP) responded monophasically when stirred with aggregating agents in the same manner as aspirin-treated normal C-PRP, but could be irreversible aggregated by high concentrations of thrombin, collagen, and ADP. Her platelets did not aggregate when stirred with AA at concentrations as high as 2 mM. Ultrastructure and levels of serotonin and adenine nucleotides wer  normal. Amounts of 14C-AA released after stirring with thrombin were similar to normal cells. However, evaluation of prostaglandin synthesis after stirring with 14C-AA revealed no evidence of endoperoxide or thromboxane production, although products of the lipoxygenase pathway were produced in normal amounts. Aggregation in response to AA was completely corrected after mixing with 10% normal C-PRP. However, equal volumes of her C-PRP and normal aspirin-treated C-PRP did not respond to AA, whereas 10% normal platelets combined with aspirin-treated cells corrected aggregation to AA. Since epinephrine pretreatment corrects the response of dog platelets that are not aggregated by AA, we evaluated the influence of epinephrine on her platelets. Preexposure to 5 micro M epinephrine, a concentration that gave only primary waves of aggregation, resulted in normalization of her response to AA, even though correction was not associated with the generation of endoperoxides or thromboxanes. The results may explain why patients with platelet cyclooxygenase deficiency have mild or absent bleeding symptoms.
D000328:Adult; D001095:Arachidonic Acids / Q000494:pharmacology*; D001792:Blood Platelets / Q000201:enzymology* / Q000378:metabolism; D004359:Drug Therapy, Combination; D004837:Epinephrine / Q000494:pharmacology*; D005260:Female; D006801:Humans; D010105:Oxygenases / Q000172:deficiency*; D010974:Platelet Aggregation / Q000187:drug effects*; D012701:Serotonin / Q000378:metabolism
D001095:Arachidonic Acids; D012701:Serotonin; D010105:Oxygenases; D004837:Epinephrine