1. Top of page
  2. Abstract

The biological functions of platelet-activating factor (PAF) have been extensively studied in the rat. However, the precise structure and distribution of rat PAF receptor has not been reported. To address this question, we isolated a rat PAF-receptor cDNA from a size-fractionated rat spleen cDNA library. The deduced amino acid sequence of the rat PAF receptor showed 80% and 79% identity with guinea pig and human PAF receptors, respectively. Pharmacological properties (ED50, inhibition by WEB2086) of rat PAF receptors expressed in Xenopus oocytes were similar to those for PAF receptors expressed from guinea pig or human cDNAs. Northern blot analysis showed a widespread distribution of PAF-receptor mRNA in almost all organs including spleen, small intestine, kidney, lung, liver and brain. Considerable difference in the PAF-receptor distribution detected among species suggests the existence of a species-specific and tissue-specific regulatory mechanism for PAF-receptor-mRNA expression. Isolation of rat PAF-receptor cDNA should facilitate further analysis of PAF-receptor function and pharmacology in diverse pathophysiological processes.


complementary RNA


central nervous system


half-maximal effective dose


heterotrimeric GTP-binding regulatory protein


open reading frame


platelet-activating factor, 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine


reverse transcriptase-polymerase chain reaction


untranslated region


  1. Top of page
  2. Abstract
  • Arai, A. & Lynch, G. (1992) Antagonists of the platelet-activating factor receptor block long-term potentiation in hippocampal slices, Eur. J. Neurosci. 4, 411419.
  • Barnes, P. J. (1991) Biochemistry of asthma, Trends Biochem. Sci. 16, 365369.
  • Benveniste, J., Henson, P. M. & Cochrane, C. G. (1972) Leukocyte-dependent histamine release from rabbit platelets. The role of IgE, basophils, and a platelet-activating factor, J. Exp. Med. 136, 13561377.
  • Benveniste, J., Tence, M., Varenne, P., Bidault, J., Boullet, C. & Polonsky, J. (1979) Semi-synthèse et structure proposee du facteur activant les plaquettes (PAF): PAF-acether, un alkyl ether analogue de la lysophosphatidylcholine, C. R. Acad. Sci. Ser. D. 289, 10371040.
  • Bito, H., Nakamura, M., Honda, Z., Izumi, T., Iwatsubo, T., Seyama, Y., Ogura, A., Kudo, Y. & Shimizu, T. (1992) Platelet-activating factor (PAF) receptor in rat brain: PAF mobilizes intracellular Ca2+ in hippocampal neurons, Neuron 9, 285294.
  • Bito, H., Kudo, Y. & Shimizu, T. (1993) Characterization of platelet-activating factor (PAF) receptor in the rat brain, J. Lipid Mediators 6, 169174.
  • Blank, M. L. Snyder, F., Byers, L. W., Brooks, B. & Muirhead, E. E. (1979) Antihypertensive activity of an alkyl ether analog of phosphatidylcholine, Biochem. Biophys. Res. Commun. 90, 11942000.
  • Braquet, P., Touqui, L., Shen, T. Y. & Vargaftig, B. B. (1987) Perspectives in platelet-activating factor research, Pharmacol. Rev. 39, 97145.
  • Caplan, M. S., Sun, X. M. & Hsueh, W. (1990) Hypoxia causes ischemic bowel necrosis in rats: the role of platelet-activating factor (PAF-acether), Gastroenterology 99, 979986.
  • Chao, W., Liu, H., Hanahan, D. J. & Olson, M. S. (1992) Platelet-activating factor-stimulated protein phosphorylation and eicosanoid synthesis in the rat Kupffer cells. Evidence for calcium-dependent and protein kinase C-dependent and -independent pathways, J. Biol. Chem. 267, 672535.
  • Chase, P. B., Halonen, M. & Regan, J. W. (1993) Cloning of a human platelet-activating factor receptor gene – evidence for an intron in the 5′-untranslated region, Am. J. Resp. Cell. Mol. Biol. 8, 240244.
  • Chirgwin, J. M., Przybyla, A. E., MacDonald, R. J. & Rutter, W. J. (1979) Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease, Biochemistry 18, 52945299.
  • Chomczynski, P. & Sacchi, N. (1987) Single-step method of RNA isolation by acid guanidium thiocyanate-phenol-chloroform extraction, Anal. Biochem. 162, 156159.
  • Clark, G. D., Happel, L. T., Zorumski, C. F. & Bazan, N. G. (1992) Enhancement of hippocampal excitatory synaptic transmission by platelet-activating factor, Neuron 9, 12111216.
  • Demopoulos, C. A., Pinckard, R. N. & Hanahan, D. J. (1979) Platelet-activating factor. Evidence for 1-O-alkyl-2-acetyl-sn-glyceryl-3-phosphorylcholine as the active component (a new class of lipid chemical mediators), J. Biol. Chem. 254, 93559358.
  • Feinberg, A. P. & Vogelstein, B. (1983) A technique for radiolabelling DNA restriction endonuclease fragments to high specific activity, Anal. Biochem. 132, 613.
  • Filep, J. G., Herman, F., Foldes-Filep, E., Schneider, F. & Braquet, P. (1992) Dexamethasone-induced gastric mucosal damage in the rat: possible role for platelet-activating factor, Br. J. Pharmacol. 105, 912918.
  • Gandhi, C. R., Stephenson, K. & Olson, M. S. (1992) A comparative study of endothelin- and platelet-activating factor-mediated signal transduction and prostaglandin synthesis in rat Kupffer cells, Biochem. J. 281, 485492.
  • Gübler, U. & Hoffman, B. J. (1983) A simple and very efficient method for generating cDNA libraries, Gene (Amst.) 25, 263269.
  • Hanahan, D. J. (1986) Platelet-activating factor: a biologically active phosphoglyceride, Annu. Rev. Biochem. 55, 483509.
  • Handa, R. K., Strandhoy, J. M. & Buckalew, V. M. Jr (1991) Selective inhibition of vasoconstrictor responses by platelet-activating factor in rat kidney, Am. J. Physiol. 29, 108116.
  • Honda, Z., Nakamura, M., Miki, I., Minami, M., Watanabe, T., Seyama, Y., Okado, H., Toh, H., Ito, K., Miyamoto, T. & Shimizu, T. (1991) Cloning by functional expression of platelet-activating factor receptor from guinea-pig lung, Nature 349, 342346.
  • Hwang, S.-B. (1990) Specific receptors of platelet-activating factor, receptor heterogeneity, and signal transduction mechanisms, J. Lipid Mediators 2, 123158.
  • Hwang, S.-B. (1991) High affinity receptor binding of platelet-activating factor in rat peritoneal polymorphonuclear leukocytes, Eur. J. Pharmacol. 196, 169175.
  • Inarrea, P., Gomez-Cambronero, J., Nieto, M. & Sanchez Crespo, M. (1984) Characterization of the binding of platelet-activating factor to platelets of different animal species, Eur. J. Pharmacol. 105, 309315.
  • Klee, A., Schmid-Schonbein, G. W. & Seiffge, D. (1991) Effects of platelet activating factor on rat platelets Escherichia coli, Eur. J. Pharmacol. 209, 223230.
  • Kornecki, E. & Ehrlich, Y. H. (1988) Neuroregulatory and neuropathological actions of the ether-phospholipid platelet-activating factor, Science 240, 17921794.
  • Kozak, M. (1987) An analysis of 5′-noncoding sequence from 699 vertebrate messenger RNAs, Nucleic Acids Res. 15, 81258148.
  • Kunz, D., Gerard, N. P. & Gerard, C. (1992) The human leukocyte platelet-activating factor receptor, J. Biol. Chem. 267, 91019106.
  • Liu, H., Chao, W. & Olson, M. S. (1992) Regulation of the surface expression of the platelet-activating factor in IC-21 peritoneal macrophages. Effects of lipopolysaccharides, J. Biol. Chem. 267, 2081120819.
  • MacNaughton, W. K. & Gall, D. G. (1991) Mechanisms of platelet-activating factor-induced electrocyte transport in the rat jejunum, Eur. J. Pharmacol. 200, 1723.
  • Massey, C. V., Kohout, T. A., Gaa, S. T., Lederer, W. J. & Rogers, T. B. (1991) Molecular and cellular actions of platelet-activating factor in rat heart cells, J. Clin. Invest. 88, 21062116.
  • Morteau, O., More, J., Pons, L. & Bueno, L. (1993) Platelet-activating factor and interleukin-1 are involved in colonic dysmotility in experimental colitis in rats, Gastroenterology 104, 4756.
  • Mutoh, H., Bito, H., Minami, M., Nakamura, M., Honda, Z., Izumi, T., Nakata R., Kurachi, Y., Terano, Y. & Shimizu, T. (1993) Two different promoters direct expression of two distinct forms of mRNAs of human platelet-activating factor receptor, FEBS Lett. 322, 129134.
  • Nakamura, M., Honda, Z., Izumi, T., Sakanaka, C., Mutoh, H., Minami, M., Bito, H., Seyama, Y., Matsumoto, T., Noma, M. & Shimizu, T. (1991) Molecular cloning and expression of platelet-activating factor receptor from human leukocytes, J. Biol. Chem. 266, 2040020405.
  • Nakamura, M., Honda, Z., Waga, I., Matsumoto T., Noma, M. & Shimizu, T. (1992) Endotoxin transduces Ca2+ signaling via platelet-activating factor receptor, FEBS Lett. 314, 125129.
  • Namm, D. H., Tadepalli, A. S. & High, J. A. (1982) Species specificity of the platelet responses to 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine, Thromb. Res. 25, 341350.
  • Perico, N. & Remuzzi, G. (1990) Role of platelet-activating factor in renal immune injury and proteinuria, Am. J. Nephrol. 10, 98104.
  • Pignol, B., Henane, S., Sorlin, B., Rola-Pleszczynski, M., Mencia-Huerta, J. M. & Braquet, P. (1990) Effect of long-term treatment with platelet-activating factor on IL-1 and II-2 production by rat spleen cells, J. Immunol. 145, 980984.
  • Prescott, S. M., Zimmerman, G. A. & McIntyre T. M. (1990) Platelet-activating factor, J. Biol. Chem. 29, 17 38117 384.
  • Rabinovici, R., Sofronski, M. D., Renz, J. F., Hillegas, Esser K. M., Vernick, J. & Feuerstein, G. (1992) Platelet activating factor mediates interleukin-2-induced lung injury in the rat, J. Clin. Invest. 89, 16691673.
  • Rayner, T. E., Menadue, M. F. & Oliver, J. R. (1991) Platelet-activating factor stimulates the release of atrial natriuretic factor from the rat heart, J. Endocrinol. 130, 281288.
  • Sambrook, J., Fritsch, E. F. & Maniatis, T. (1989) Molecular cloning: a laboratory manual, 2nd edn, Cold Spring Harbor Laboratory Press, Cold Spring Harbor NY .
  • Sanger, F., Nicklen, S. & Coulson, A. R. (1977) DNA sequencing with chain-terminating inhibitors, Proc. Natl Acad. Sci. USA 74, 54635467.
  • Seyfried, C. E., Schweickart, V. L., Godiska, R. & Gray, P. W. (1992) The human platelet-activating factor receptor gene (PTAFR) contains no introns and maps to chromosome 1, Genomics 13, 832834.
  • Shimizu, T. (1992) Molecular cloning of platelet-activating factor receptors, in PAF receptor signal mechanism (Shukla, S. D., ed.) pp. 2940, C. R. C. Press, Florida .
  • Shimizu, T., Honda, Z., Nakamura, M., Bito, H. & Izumi, T. (1992) Biochem. Pharmacol. 44, 10011008.
  • Shukla, S. D., Buxton, D. B., Olson, M. & Hanahan, D. J. (1983) Acetylglyceryl ether phosphocholine: a potent activator of hepatic phosphoinositide metabolism and glycogenolysis, J. Biol. Chem. 29, 10 21210 214.
  • Snyder, F. (1989) Biochemistry of platelet-activating factor: a unique class of biologically active phospholipids, Proc. Soc. Exp. Biol. Med. 190, 125135.
  • Squinto, S. P., Block, A. L., Braquet, P. & Bazan, N. Z. (1989) Platelet-activating factor stimulates Fos/Jun/AP-1 transcription signaling system in human neuroblastoma cells, J. Neurosci. Res. 24, 558566.
  • Sugimoto, T., Tsuchimochi, H., McGregor, C. G. A., Mutoh, H., Shimizu, T. & Kurachi Y. (1992) Molecular cloning and characterization of the platelet-activating factor receptor gene expressed in the human heart, Biochem. Biophys. Res. Commun. 189, 617624.
  • Waga, I., Nakamura, M., Honda, Z., Ferby, I., Toyoshima, S., Ishiguro, S. & Shimizu, T. (1993) Distinct signal transduction pathways by endotoxin for the activation of guinea pig macrophages and neutrophils, Biochem. Biophys. Res. Commun. 197, 465472.
  • Wood, D. A., Hapak, L. K., Sims, S. M. & Dixon, S. J. (1991) The direct effects of PAF on isolated rat osteoclasts, J. Biol. Chem. 29, 15 36915 376.
  • Wieraszko, A., Li, G., Kornecki, E., Hogan, M. V. & Ehrlich, Y. H. (1993) Long-term potentiation in the hippocampus induced by platelet-activating factor, Neuron 10, 553557.
  • Ye, R. D., Prossnitz, E. R., Zou, A. & Cochrane, C. G. (1991) Characterization of a human cDNA that encodes a functional receptor for platelet activating factor, Biochem. Biophys. Res. Commun. 180, 105111.