Platelet-activating factor (PAF, 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) is a biologically active phospholipid mediator. Although PAF was named for its potential to induce platelet aggregation, intense investigations have elucidated potent biological actions of PAF in a broad range of cell types and tissues. PAF acts by binding to a unique G-protein-coupled seven transmembrane receptor, and activates multiple intracellular signaling pathways. In the last decade, we have identified the PAF receptor structures, intracellular signaling mechanisms, and genomic organizations. Recently, we found a single nucleotide polymorphism of the human PAF receptor (A224D) with an allele frequency of 7.8% in Japanese. Cells expressing this receptor exhibited the reduced cellular signaling, although the binding parameters remain unchanged. We have established two different types of genetically altered mice, i.e. PAF receptor-overexpressing mouse and PAF receptor-deficient mouse. These mutant mice provide a novel and specific approach for identifying the pathophysiological and physiological functions of PAF in vivo. This review focuses on phenotypes of these mutant mice and summarizes the previous reports regarding PAF and PAF receptor. (C) 2002 Elsevier Science Inc. All rights reserved.
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Univ Tokyo, Fac Med, Dept Allergy, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1138655, JapanUniv Tokyo, Fac Med, Dept Allergy, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1138655, Japan
Honda, Z
Ishii, S
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机构:Univ Tokyo, Fac Med, Dept Allergy, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1138655, Japan
Ishii, S
Shimizu, T
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机构:Univ Tokyo, Fac Med, Dept Allergy, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1138655, Japan
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Univ Southampton, Southampton Gen Hosp, Surg Unit, Southampton SO16 6YD, Hants, EnglandUniv Southampton, Southampton Gen Hosp, Surg Unit, Southampton SO16 6YD, Hants, England