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Vol. 55, Issue 1, 195-227, March 2003
,
Centre National de la Recherche Scientifique UMR 7131, Hôpital Broussais, Bâtiment René Leriche, Paris,
France (C.B.); Unit for Experimental Asthma and Allergy, The National
Institute of Environmental Medicine, Karolinska Institutet, Stockholm,
Sweden (S.-E. D.); Harvard Medical School, Brigham and Woman's
Hospital, Boston, Massachusetts (J.M.D.); Department of Pharmacology,
Merck & Co., West Point, Pennsylvania (J.F.E.); GlaxoSmithKline, King
of Prussia, Pennsylvania (D.W.P.H.); Division Molecular Pharmacology,
Pharmacological Sciences, Milan, Italy (S.N.); Center for Experimental
Therapeutics and Reperfusion Injury, Department of Anesthesia Research
Laboratory, Brigham and Woman's Hospital/Harvard Medical School,
Boston, Massachusetts (C.N.S.); Department of Biochemistry and
Molecular Biology, Faculty of Medicine, University of Tokyo, Tokyo,
Japan (T.S., T.Y.)
I. Introduction
II. General Considerations
A. Biochemical Pathways
B. Cellular Origins
C. Nomenclature for Leukotriene Receptors
III. Molecular Database for Leukotriene Receptors
A. Molecular and Structural Aspects of Dihydro-Leukotriene
Receptors
1. BLT1.
2. BLT2.
3. Phenotypes Involving BLT Receptors.
B. Molecular and Structural Aspects of Cysteinyl-Leukotriene
Receptors
1. CysLT1.
2. CysLT2.
C. Lipoxin Receptors
1. Molecular and Structural Aspects of Lipoxin
Receptors.
D. Receptors and Cellular Signals
1. BLT.
2. CysLT.
3. Lipoxins.
E. Summary
IV. Properties and Significance of Leukotriene Receptors
A. BLT Functional and Radioligand Binding Studies
B. Cysteinyl-Leukotriene Functional Studies
1. Airway Smooth Muscle Contraction.
2. Vascular Smooth Muscle Contraction.
3. Vascular Smooth Muscle Relaxation.
4. Cardiovascular Effects.
5. Diverse Effects of Cysteinyl-Leukotrienes.
C. CysLT Radioligand Binding Studies
1. [3H]LTC4 Binding Sites.
2. [3H]LTD4 Binding Sites.
D. Evidence for Additional CysLT Receptor Subtypes
E. Clinical Studies Involving CysLT Receptors
F. Summary
G. Lipoxins Receptors
1. Functional and Radioligand Binding Studies.
2. Summary.
V. General Conclusions
References
The leukotrienes and lipoxins are biologically active metabolites derived from arachidonic acid. Their diverse and potent actions are associated with specific receptors. Recent molecular techniques have established the nucleotide and amino acid sequences and confirmed the evidence that suggested the existence of different G-protein-coupled receptors for these lipid mediators. The nomenclature for these receptors has now been established for the leukotrienes. BLT receptors are activated by leukotriene B4 and related hydroxyacids and this class of receptors can be subdivided into BLT1 and BLT2. The cysteinyl-leukotrienes (LT) activate another group called CysLT receptors, which are referred to as CysLT1 and CysLT2. A provisional nomenclature for the lipoxin receptor has also been proposed. LXA4 and LXB4 activate the ALX receptor and LXB4 may also activate another putative receptor. However this latter receptor has not been cloned. The aim of this review is to provide the molecular evidence as well as the properties and significance of the leukotriene and lipoxin receptors, which has lead to the present nomenclature.
During the preparation of this manuscript, Professor Nicosia passed
away following a long illness. Her efforts in the organization of this
committee and her scientific work on the leukotriene receptors over the
past years will be missed.
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