Long-lived enzymatic metabolites of thromboxane B2 in the human circulation |
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| Affiliation: | 1. The Department of Pharmacology, Vanderbilt University, Nashville, Tennessee 37232 USA;2. The Department of Pharmacology, Catholic University, Rome, Italy;1. S3 119, Schurman Hall, College of Veterinary Medicine, Cornell University, Ithaca, NY 14850, USA;2. Department of Population Medicine & Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA;3. GD Animal Health, Deventer, The Netherlands;4. Department of Animal Sciences, Wageningen University, Wageningen,The Netherlands;1. University of South Australia, School of Pharmacy and Medical Sciences, North Terrace, Adelaide, South Australia, 5000, Australia;2. Centre for Cancer Biology, University of South Australia and SA Pathology, Frome Road, Adelaide, SA 5000, Australia;1. S3 119, Schurman Hall, College of Veterinary Medicine, Cornell University, Ithaca, NY 14850, United States;2. Department of Population Medicine & Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, United States;3. GD Animal Health, Deventer, The Netherlands;4. Department of Animal Sciences, Wageningen University, Wageningen, The Netherlands;1. Institute of Cardiovascular Research and Sports Medicine, Department of Molecular and Cellular Sports Medicine, German Sport University, Cologne, Germany;2. Department of Safety and Quality of Fruit and Vegetables, Max Rubner-Institut, Karlsruhe, Germany, Germany;3. State Key Laboratory of Food Science and Technology, Nanchang University, China;4. Clinic for Cattle, Endocrinology, University of Veterinary Medicine, Hannover, Germany;1. Department of Lipid Chemistry, National Institute of Nutrition, Indian Council of Medical Research, Hyderabad, India;2. Department of Pathology, National Institute of Nutrition, Indian Council of Medical Research, Hyderabad, India |
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| Abstract: | Thromboxane A2, a potent vasoconstrictor and platelet agonist, is an evanescent cyclooxygenase product of arachidonic acid. Assessment of thromboxane biosynthesis commonly relies upon analysis of the stable but biologically inactive hydration product, thromboxane B2. However, measurement of this compound in plasma is readily confounded by platelet activation ex vivo. We have identified 11-dehydro-thromboxane B2, 11-dehydro-13,14-dihydro-15-keto-thromboxane B2, and 2,3-dinor-thromboxane B2 as enzymatic products of infused thromboxane B2 in the human circulation. Biosynthesis of deuterated standards permitted the development of quantitative analyses for these compounds, employing capillary gas chromatography-negative ion chemical ionization-mass spectrometry. We thus established that the postinfusion half-lives of 11-dehydrothromboxane B2 and the keto-dihydro metabolite approximated 1 hour, while that of the dinor metabolite ranged from 15 to 17 min. Combined analysis of short- and long-lived enzymatic metabolites of thromboxane B2 promises to bypass the problem of ex vivo platelet activation and enhance the likelihood of relating a discreet clinical event to an alteration in the biosynthesis of thromboxane A2 in the human circulation. |
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