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Platelet Activating Factor and Results of PAF Antagonist Therapy

  • A. N. Kingsnorth

Abstract

Platelet activating factor (PAF) is a phospholipid released from cell membranes by the action of phospholipase A2 and it has been implicated in a variety of pathophysiological disorders including acute pancreatitis (1,2). The development of potent PAF receptor antagonists has lead to a greater understanding of the role of PAF in disease processes and the potential for development of these compounds as therapy for inflammatory diseases (3,4). PAF (1-0-alkyl-2-acetyl-sn-glycero-3-phosphocholine) was the term originally introduced for a soluble platelet aggregating substance released from IgE stimulated basophils. PAF is a component of structural membrane lipids and together with other classes of lipid mediators such as arachidonates and leukotrienes, it is involved in the trafficking of membrane phospholipids via transacetylation reactions. PAF is involved in both physiological (fertilisation, foetal development, pressor activity) and pathological processes such as asthma, ischaemia, the systemic inflammatory response syndrome, multiple organ failure and pancreatitis.

Keywords

Acute Pancreatitis Organ Failure Platelet Activate Factor Severe Acute Pancreatitis Platelet Activate Factor Antagonist 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Formela LJ, Galloway SW, Kingsnorth AN (1995) Inflammatory mediators in acute pancreatitis. Br J Surg 82:6–13.PubMedCrossRefGoogle Scholar
  2. 2.
    Kingsnorth AN (1997) Role of cytokines and their inhibitors in acute pancreatitis. Gut 40:1–4.PubMedGoogle Scholar
  3. 3.
    Venable ME, Zimmerman GA, Mclntyre TM, Prescott SM (1993) Platelet activating factor: a phospholipid autacoid with diverse actions. J Lipid Res 34:691–702.PubMedGoogle Scholar
  4. 4.
    Koltai M, Guinot P, Hosford D, Braquet PG (1994) Platelet activating factor antagonists: scientific background and possible clinical applications. Adv Pharmacol 28:81–167.PubMedCrossRefGoogle Scholar
  5. 5.
    Banerjee AK, Galloway SW, Kingsnorth AN (1994) Experimental models of acute pancreatitis. Br J Surg 81:1096–1103.PubMedCrossRefGoogle Scholar
  6. 6.
    Soling H-D, Fest W (1986) Synthesis of l-0-alkyl-2-acetyl-sn-glycero-3-phosphocholine (platelet-activating factor) in exocrine glands and its control by secretagogues. J Biol Chem 261:13916–13922.PubMedGoogle Scholar
  7. 7.
    Emanuelli G, Montrucchio G, Gaia E, Dughera L, Corvelli G, Gubetta L (1989) Experimental acute pancreatitis induced by platelet-activating factor in rabbits. Am J Pathol 134:315–326.PubMedGoogle Scholar
  8. 8.
    Emanuelli G, Montrucchio G, Dughera L et al. (1994) Role of platelet activating factor in acute pancreatitis induced by lipopolysaccharides in rabbits. Eur J Pharmacol 261:265–272.PubMedCrossRefGoogle Scholar
  9. 9.
    Konturek SJ, Dembinski A, Konturek PJ et al. (1992) Role of platelet activating factor in pathogenesis of acute pancreatitis in rats. Gut 33:1268–1274.PubMedCrossRefGoogle Scholar
  10. 10.
    Ais G, Lopez-Farre A, Gomez-Garre DN et al. (1992) Role of platelet activating factor in hemodynamic derangements in an acute rodent pancreatic model. Gastroenterology 102:181–187.PubMedGoogle Scholar
  11. 11.
    Tomaszewska R, Dembiniski A, Warzecha Z, Banas M, Konturek SJ, Stachura J (1992) Platelet activating factor (PAF) inhibitor (TCV-309) reduces caerulein and PAF-induced pancreatitis. A morphologic and functional study in the rat. J Physiol Pharmacol 4:345–352.Google Scholar
  12. 12.
    Dabrowski A, Gabrylelewicz A, Chyczewski L (1991) The effect of platelet activating factor antagonist (BN52021) on cerulein induced acute pancreatitis with reference to oxygen radicals. Int J Pancreatol 8:1–11.PubMedGoogle Scholar
  13. 13.
    Yotsumoto L, Manabe T, Kyogoku T et al. (1994) Platelet-activating factor involvement in the aggravation of acute pancreatitis in rabbits. Digestion 55:260–267.PubMedCrossRefGoogle Scholar
  14. 14.
    Zhou W, McCollum MO, Levine BA, Olson MS (1992) Role of platelet-activating factor in pancreatitis associated acute lung injury in the rat. Am J Pathol 140:971–979.PubMedGoogle Scholar
  15. 15.
    Kald B, Kald A, Ihse I, Tagesson C (1993) Release of platelet-activating factor in acute experimental pancreatitis. Pancreas 8:440–442.PubMedCrossRefGoogle Scholar
  16. 16.
    Galloway SW, Kingsnorth AN (1996) Lung injury in microembolic model of acute pancreatitis. Pancreas 13:140–146.PubMedCrossRefGoogle Scholar
  17. 17.
    Whittaker M (1992) PAF receptor antagonists: recent advances. Curr Opin Ther Patents 2:583–623.CrossRefGoogle Scholar
  18. 18.
    Formela LJ, Wood LM, Whittaker M, Kingsnorth AN (1994) Amelioration of acute pancreatitis in a rat model by a potent platelet activating factor antagonist. Br J Surg 81:1783–1785.PubMedCrossRefGoogle Scholar
  19. 19.
    Kingsnorth AN, Galloway SW, Formela LJ (1995) Randomized, double-blind Phase II trial of lexipafant, a platelet activating factor antagonist, in human acute pancreatitis. Br J Surg 82:1414–1420.PubMedCrossRefGoogle Scholar
  20. 20.
    Nathens AB, Marshall JC (1996) Sepsis, SIRS and MODS: what’s in a name? World J Surg 20:386–391.PubMedCrossRefGoogle Scholar
  21. 21.
    McKay C, Curran F, Sharpies, Imine CW (1997) A placebo controlled randomised study of lexipafant in severe acute pancreatitis. Br J Surg 84 (in press).Google Scholar
  22. 22.
    Toh SKC and The British Acute Pancreatitis Study Group (1997) Lexipafant, a platelet activating factor antagonist, reduces mortality in a randomised placebo controlled study in patients with severe acute pancreatitis. Gut 40 (suppl 1): A12.Google Scholar

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© Springer-Verlag London Limited 1999

Authors and Affiliations

  • A. N. Kingsnorth

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