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Recent advances in the management of asthma using leukotriene modifiers.

Nomenclature for leukotriene and lipoxin receptors. International Union of Pharmacology XXXVII. Basic principles and clinical correlates.В Philadelphia Lipincott Williams & Williams 1999.ДЄsthma and leukotrienes: antileukotrienes as novel anti-asthmatic drugs.Д«rinkВ C, DahlenВ SВ E, DrazenВ J, EvansВ JВ F, HayВ DВ W, NicosiaВ S. Lipoxins and aspirin-triggered 15-epi-lipoxins.В In: Gallin JL, Syndermann R, editors Inflammation. Prostaglandins and leukotrienes: advances in eicosanoid biology.ДҐ-lipoxygenase: cellular biology and molecular pharmacology.Д®icosanoid transcellular biosynthesis: from cell-cell interactions to in vivo tissue responses. MAPEG:membrane-associated proteins in eicosanoid andДЇMLP: N-formyl-methionyl-leucyl-phenylalanineДҐ-Lipoxygenase - arachidonic acid - leukotrienes - leukocytes - inflammation - plants - natural compounds - inhibitors References H(P)ETE:hydro(pero)xyeicosatetraenoic acid In the second part, natural compounds that interfere with 5-LO product formation are compiled and grouped into structural classes, and the underlying molecular mechanisms and structure-activity relationships are discussed. In the first part of this review, the biology and molecular pharmacology of the 5-LO pathway is summarized in order to understand its overall regulation and complexity as well as to comprehend the possible points of attack of compounds that eventually lead to inhibition of 5-LO product formation in intact cells. However, many investigations have addressed the efficacy of a given compound solely in cellular test systems and analysis of direct interference with 5-LO has been neglected. To date, a huge number of diverse plant-derived compounds have been reported to interfere with 5-LO product synthesis. Natural or plant-derived substances were among the first 5-LO inhibitors identified in the early 1980 s. Pharmacological and genetic interruption of the 5-LO pathway or blockade of LT receptors, serving as means for intervention with LTs, may be of therapeutic value for certain related disorders.

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LTs have prominent functions in pathophysiology and are connected to numerous disorders including bronchial asthma, allergic rhinitis, inflammatory bowel and skin diseases, rheumatoid arthritis, cancer, osteoporosis and cardiovascular diseases. Subsequent enzymatic conversion of LTA 4 yields LTB 4 and the cysteinyl-LTs C 4, D 4 and E 4.

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The biosynthesis of leukotrienes (LTs) is initiated by the transformation of free arachidonic acid to LTA 4 by 5-lipoxygenase (5-LO).

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