Thromboxane biosynthesis in allergen-induced bronchospasm. Evidence for platelet activation.
To determine if platelet activation occurs after allergen inhalation in atopic asthmatics, we measured two urinary metabolites of the principal cyclooxygenase product of platelets, thromboxane A2 (TxA2), using the sensitive and specific technique of gas chromatography-negative ion, chemical ionization-mass spectrometry. Seven atopic asthmatics underwent allergen challenge after low dose aspirin to suppress platelet thromboxane generation and on placebo days. On placebo days, the urinary levels of 2,3-dinor-TxB2 increased from 76 +/- 22 pg/mg creatinine to 216 +/- 95 after allergen, and 11-dehydro-TxB2 from 396 +/- 98 to 627 +/- 137 (p less than 0.05). Low dose aspirin suppressed excretion of urinary thromboxane metabolites and prevented the rise after allergen inhalation without altering the bronchoconstriction. Excretion of 2,3-dinor-6-keto-PGF1 alpha, a metabolite of prostacyclin, was unaltered by this aspirin regimen. We conclude that platelets are activated after allergen challenge, but that platelet-derived TxA2 is not important in the early bronchoconstrictor response.
Lupinetti
M D
MD
Division of Clinical Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee.
Sheller
J R
JR
Catella
F
F
Fitzgerald
G A
GA
D015121:6-Ketoprostaglandin F1 alpha / Q000652:urine / Q000031:analogs & derivatives; D000328:Adult; D000485:Allergens; D001241:Aspirin / Q000494:pharmacology; D001792:Blood Platelets / Q000201:enzymology; D001986:Bronchial Spasm / Q000097:blood* / Q000503:physiopathology; D002986:Clinical Trials as Topic; D016861:Cyclooxygenase Inhibitors; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects / Q000502:physiology; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D008297:Male; D010919:Placebos; D015539:Platelet Activation / Q000502:physiology*; D013928:Thromboxane A2 / Q000096:biosynthesis*; D013929:Thromboxane B2 / Q000652:urine / Q000031:analogs & derivatives
D000485:Allergens; D016861:Cyclooxygenase Inhibitors; D010919:Placebos; D013929:Thromboxane B2; D013928:Thromboxane A2; D015121:6-Ketoprostaglandin F1 alpha; C028965:2,3-dinor-thromboxane B2; C028290:2,3-dinor-6-ketoprostaglandin F1alpha; C049235:11-dehydro-thromboxane B2; D001241:Aspirin