DETECTION OF THE MAJOR URINARY METABOLITE OF PROSTAGLANDIN D-2 IN THE CIRCULATION - DEMONSTRATION OF ELEVATED LEVELS IN PATIENTS WITH DISORDERS OF SYSTEMIC MAST-CELL ACTIVATION

The symptoms and hemodynamic alterations chat accompany episodes of systemic mast cell activation have been largely attributed to excessive prostaglandin (PG)D-2 release. Quantification of the major urinary metabolite of PGD(2) has been invaluable in elucidating a role for PGD(2) in these clinical entities and in the biochemical evaluation of systemic mastocytosis. With the use of a modified mass spectrometric assay for the major urinary metabolite of PGD(2), this metabolite was detected in plasma from 10 normal volunteers (3.5 +/- 1.4 pg/ml). Ingestion of niacin, which induces endogenous release of PGD(2), increased plasma levels of this metabolite 6.3 to 33 times above the upper limit of normal by 2 hours. Thereafter levels declined gradually but remained elevated for lip to 6 to 8 hours. In contrast circulating levels of 9 alpha,11 beta-PGF(2), the initial metabolite of PGD(2), peaked by 30 minutes and returned to baseline by 2 hours. The clinical utility of measuring the major urinary metabolite in the circulation was demonstrated by detection of markedly increased levels in plasma and serum from patients with systemic mastocytosis and a patient with a severe type I allergic reaction. Thus in the biochemical evaluation of episodes of systemic mast cell activation and endeavors to further elucidate the role of PGD(2) in human disease, there are kinetic advantages of measuring the major urinary metabolite of PGD(2) in the circulation. One particular advantage is the evaluation of clinical events, which only in retrospect are suspected to be associated with excessive release of PGD(2), yet plasma or serum was obtained proximate to the event.