Cloning by functional expression of platelet-activating factor receptor from guinea-pig lung

PLATELET-activating factor (PAF), a unique phospholipid mediator, possesses potent proinflammatory, smooth-muscle contractile and hypotensive activities, and appears to be crucial in the pathogenesis of bronchial asthma and in the lethality of endotoxin and anaphylactic shock1–3. Despite this, little is known of the molecular properties of the PAF receptor and related signal transduction systems. Although several lines of evidence suggest that activation of the PAF receptor stimulates phospholipase C and subsequent inositol trisphosphate formation through G protein(s)4,5, the PAF receptor and calcium channel are reported to show a close relation2,6. As a first approach to cloning lipid autacoid receptors, we have isolated complementary DNA for the PAF receptors. Our strategy involved gene expression in Xenopus laevis oocytes and electrophysiological detection of PAF-induced responses. Sequence analysis indicates that the receptor belongs to the superfamily of G protein-coupled receptors.

[1]  B. Barrell,et al.  Human cytomegalovirus encodes three G protein-coupled receptor homologues , 1990, Nature.

[2]  M. Parmentier,et al.  Molecular cloning of the thyrotropin receptor. , 1989, Science.

[3]  J. C. Robbins,et al.  The Chemical and Biological Properties of PAF Agonists, Antagonists, and Biosynthetic Inhibitors , 1987 .

[4]  Y. Ehrlich,et al.  Neuroregulatory and neuropathological actions of the ether-phospholipid platelet-activating factor. , 1988, Science.

[5]  M. Caron,et al.  A family of receptors coupled to guanine nucleotide regulatory proteins. , 1987, Biochemistry.

[6]  Brian K. Kobilka,et al.  Cloning of the gene and cDNA for mammalian β-adrenergic receptor and homology with rhodopsin , 1986, Nature.

[7]  Takao Shimizu,et al.  Arachidonic Acid Cascade and Signal Transduction , 1990, Journal of neurochemistry.

[8]  S. Pong,et al.  Ionic and GTP regulation of binding of platelet-activating factor to receptors and platelet-activating factor-induced activation of GTPase in rabbit platelet membranes. , 1986, The Journal of biological chemistry.

[9]  P. Seeburg,et al.  Lutropin-choriogonadotropin receptor: an unusual member of the G protein-coupled receptor family. , 1989, Science.

[10]  Y. Imura,et al.  CV-6209, a highly potent antagonist of platelet activating factor in vitro and in vivo. , 1987, The Journal of pharmacology and experimental therapeutics.

[11]  J. O'flaherty,et al.  Platelet-Activating Factor: Mechanisms of Cellular Activation , 1987 .

[12]  J. Travers,et al.  Identification of functional platelet-activating factor receptors in Raji lymphoblasts. , 1989, Journal of immunology.

[13]  K. Weber,et al.  Pharmacological actions of WEB 2086, a new specific antagonist of platelet activating factor. , 1987, The Journal of pharmacology and experimental therapeutics.

[14]  H. Sarau,et al.  Platelet-activating factor-induced phosphoinositide metabolism in differentiated U-937 cells in culture. , 1989, The Journal of pharmacology and experimental therapeutics.

[15]  P. Barnes,et al.  [3H]WEB 2086 labels platelet activating factor receptors in guinea pig and human lung. , 1989, European journal of pharmacology.

[16]  D. Hanahan.  Platelet activating factor: a biologically active phosphoglyceride. , 1986, Annual review of biochemistry.

[17]  J. Nathans,et al.  Isolation, sequence analysis, and intron-exon arrangement of the gene encoding bovine rhodopsin , 1983, Cell.

[18]  K. Chung,et al.  Characterization of platelet‐activating factor‐induced elevation of cytosolic free calcium concentration in eosinophils , 1989, FEBS letters.

[19]  S. Nakanishi,et al.  cDNA eloping of bovine substance-K receptor through oocyte expression system , 1987, Nature.

[20]  B. Habecker,et al.  Isolation, sequence, and functional expression of the mouse M1 muscarinic acetylcholine receptor gene. , 1988, The Journal of biological chemistry.

[21]  D. Grandy,et al.  Cloning and expression of a rat D2 dopamine receptor cDNA , 1988, Nature.

[22]  H. Hayashi,et al.  Activation of guinea pig peritoneal macrophages by platelet activating factor (PAF) and its agonists. , 1985, Journal of biochemistry.