Bengt Samuelsson

Karolinska Institutet

Primary Section: 21, Biochemistry
Membership Type: International Member (elected 1984)

Research Interests

Prostaglandins and leukotrienes: The prostaglandins as well as the more recent members of this group of compounds, thromboxanes and leukotrienes, are formed from arachidonic acid by oxygenation and further transformation. The oxygenated derivatives control a variety of cellular functions. Thromboxane A2 is a potent constrictor of blood vessels and also causes aggregation of blood platelets. This is of importance in the clotting process but the thromboxanes also play an important role in the pathological counterpart, viz. thrombosis. This occurs in heart attacks and strokes. A prostaglandin with opposite effects, prostacyclin, is formed by the blood vessels and there is a homeostatic control mechanism based on these compounds. Other prostaglandins have additional functions related to inflammation, regulation of blood pressure and electrolyte metabolism and reproduction. Subsequently, a new group of biologically active compounds, the leukotrienes, was discovered in our laboratories. These compounds are formed from arachidonic acid via a lipoxygenase pathway. Leukotriene C4 and D4 are potent bronchoconstrictors, increase vascular permeability and stimulate mucus secretion. They are formed in lung tissue of asthmatic subjects on exposure to allergens and seem to be responsible for the symptoms in asthma. Other leukotrienes have pro-inflammatory effects and stimulate the migration of leukocytes. This is of importance for the host defense system of the body. Knowledge about the structures, biological role and formation of these arachidonic acid derivatives has opened up new avenues for development of novel therapeutic principles. These include the use of prostaglandins for induction of labor and fertility control, treatment of gastric ulcers, peripheral vascular disease and glaucoma. Inhibitors of prostaglandin and thromboxane formation are of importance in the development of anti-inflammatory drugs and drugs for treatment or prevention of thrombotic events as in heart attacks and strokes. Inhibitors of leukotriene formation or antagonists of leukotrienes are now used as drugs for treatment of asthma. They are also studied in other allergic conditions as well as psoriasis and various inflammatory diseases.

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