| Citation | Bengt Samuelsson shared the Nobel prize in Physiology or Medicine in 1982 for discoveries concerning prostaglandins and related biologically active substances. As a pioneer in this field in the 1960's he participated in the characterization of the structure of the prostaglandins and in the discovery that their precursors were essential fatty acids such as arachidonic acid. He demonstrated that the enzymic oxygenation of arachidonic acid was initiated by withdrawal of a hydrogen at carbon 13. He then demonstrated that both of the oxygen atoms on the prostaglandin ring were derived from a single molecule of oxygen. He confirmed his speculation that prostaglandins were formed from a common intermediate by the isolation and identification of two endoperoxides, PGG2 and PGH2, which he showed to be precursors of prostaglandins D, E, and F.
Knowing that aspirin blocked prostaglandin biosynthesis, and that inhibition of platelet aggregation by aspirin could not be explained by the known prostaglandings, Samuelsson showed that the endoperoxides aggregated platelets. This led to his discovery that the major pathway of endoperoxide metabolism in the platelet was to a novel compound, which he named thromboxane A2. Thromboxane A2 was a more potent stimulus for platelet aggregation than the endoperoxides. Thromboxane antagonists and synthetase inhibitors are now being tested as anti-thrombotic drugs.
Corticosteroids inhibit the release of arachidonic acid by phospholipase and have anti-inflammatory effects not shared by the aspirin-like drugs. This suggested to Samuelsson that arachidonic acid was metabolised to important products by enzymes other than cyclo-oxygenase. He examined polymorpho-nuclear leukocytes, cells central to many inflammatory processes and discovered that arachidonic acid was metabolised by a 5-lipoxygenase to a series of products which he called leukotrienes (LTs). One of these, LTB4, has subsequently been found to be a potent chemotactic agent for leukocytes.
Slow reacting substance of anaphylaxis (SRS-A), originally detected by Feldberg and Kellaway in 1930, is released during anaphylaxis, an implicated as a mediator of bronchoconstriction in asthma. Samuelsson and his colleagues studied the biosynthesis of SRS-A in mast cells and found that one of the SRS-A's was derived from the conjugation of gluthathione with the leukotriene epoxide LTA4. The glutathionyl conjugate, named LTC4 was a potent bronchoconstrictor. The discovery of the leukotrienes has provided a basis for synthesis inhibitors and antagonists to be tested as anti-inflammatory and anti-asthmatic drugs.
In recent studies, Samuelsson has characterized new tri-hydroxy derivatives of arachidonic acid which he called lipoxins. The lipoxins inhibit the cytotoxic reaction of natural killer T-cells, but they do not affect their binding to target cells. Lipoxin A also caused degranulation of leukocytes and contraction of bronchial smooth muscle.
Elucidation of the oxygenated metabolites of arachidonic acid and their biological importance has contributed substantially to many fields of medicine. It also has provided a basis for the development of new knowledge and therapy in the future.
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