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Home / Equine Research Bank / Proc Natl Acad Sci U S A / Platelet-activating factor stimulates metabolism of phosphoi...
Proceedings of the National Academy of Sciences of the United States of America1983; 80(4); 965-968; doi: 10.1073/pnas.80.4.965

Platelet-activating factor stimulates metabolism of phosphoinositides in horse platelets: possible relationship to Ca2+ mobilization during stimulation.

Abstract: Stimulation of horse platelets with platelet-activating factor (PAF) induces a rapid degradation of phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2]. Addition of 0.1 microM PAF for 5 sec to platelets prelabeled with 32P induces a 50% loss of [32P]PtdIns(4,5)P2. 32P-Labeled phosphatidylinositol 4-monophosphate (PtdIns4P) and [32P]phosphatidylinositol (PtdIns) also are decreased, albeit at a slower rate. Loss of 32P radioactivity correlates with a net loss of fatty acids from both polyphosphoinositides. Stimulation of platelets with PAF also produces formation of [32P]phosphatidic acid and [32P]lysophosphatidylinositol. The initial disappearance of inositol lipids is subsequently followed by resynthesis, as evidenced by increased incorporation of 32P into PtdIns(4,5)P2, PtdIns4P, and PtdIns. The resynthesis of the inositides increases with time and is proportional to the concentration of PAF. Prostacyclin (1 microM) inhibits (i) the formation of phosphatidic acid and lysophosphatidylinositol and (ii) the resynthesis of polyphosphoinositides induced by 0.03 microM PAF without affecting the initial loss of PtdIns(4,5)P2. The loss of inositol lipids appears to be a primary event of platelet activation. The initial loss of polyphosphoinositides might be linked to the initiation of cellular activation by mobilizing membrane-bound Ca2+, whereas the subsequent formation of these lipids might be involved in mechanisms to prevent overstimulation of the cell.
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Publication Date: 1983-02-01 PubMed ID: 6341992PubMed Central: PMC393508DOI: 10.1073/pnas.80.4.965Google Scholar: Lookup
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  • Journal Article

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research investigates the role of platelet-activating factor (PAF) in horse platelets, specifically the way it brings about degradation of phosphatidylinositol 4,5-bisphosphate and impacts calcium mobilization.

Stimulation of Horse Platelets with PAF

  • The study starts by exploring how PAF stimulates horse platelets. It is found that addition of 0.1 microM PAF for 5 seconds catalyzes a loss of 50% of phosphatidylinositol 4,5-bisphosphate (a type of phosphoinositide).
  • Other phosphoinositides like phosphatidylinositol 4-monophosphate and phosphatidylinositol are also decreased but at a slower rate.
  • The researchers were able to track this through the loss of 32P radioactivity that correlates with the net loss of fatty acids from polyphosphoinositides.

Formation of Phosphatidic Acid and Lysophosphatidylinositol

  • Beyond the loss of phosphoinositides, stimulation of platelets with PAF generates phosphatidic acid and lysophosphatidylinositol.
  • These newly formed components suggest that the action of PAF doesn’t end in destruction of phosphoinositides, but also includes the formation of other components.

Resynthesis of Inositol Lipids

  • Following the initial disappearance of inositol lipids, resynthesis occurs. This is signified by an increased incorporation of 32P into phosphatidylinositol 4,5-bisphosphate, phosphatidylinositol 4-monophosphate, and phosphatidylinositol.
  • The rate of this resynthesis increases over time and is in proportion to the concentration of PAF added.

Role of Prostacyclin

  • The research also points to the role of prostacyclin, which inhibits both the formation of phosphatidic acid, lysophosphatidylinositol, and the resynthesis of polyphosphoinositides induced by PAF. However, it doesn’t affect the initial loss of phosphatidylinositol 4,5-bisphosphate.

Conclusions Drawn

  • It’s suggested that this loss of inositol lipids may be a primary event in platelet activation.
  • Also, the initial loss of polyphosphoinositides may link to the start of cellular activation by mobilizing membrane-bound Calcium.
  • Simultaneously, the later formation of these lipids seems to play a part in mechanisms that seek to prevent over-excitement of the cell.

Cite This Article

APA
Billah MM, Lapetina EG. (1983). Platelet-activating factor stimulates metabolism of phosphoinositides in horse platelets: possible relationship to Ca2+ mobilization during stimulation. Proc Natl Acad Sci U S A, 80(4), 965-968. https://doi.org/10.1073/pnas.80.4.965

Publication

Proceedings of the National Academy of Sciences of the United States of America
ISSN: 0027-8424
NlmUniqueID: 7505876
Country: United States
Language: English
Volume: 80
Issue: 4
Pages: 965-968

Researcher Affiliations

Billah, M M
    Lapetina, E G

      MeSH Terms

      • Animals
      • Blood Platelets / metabolism
      • Calcium / metabolism
      • Epoprostenol / metabolism
      • Horses
      • Membrane Lipids / metabolism
      • Phosphatidylinositols / metabolism
      • Phospholipases / metabolism
      • Phospholipids / metabolism
      • Platelet Activating Factor / pharmacology

      References

      This article includes 35 references
      1. Polonsky J, Tencé M, Varenne P, Das BC, Lunel J, Benveniste J. Release of 1-O-alkylglyceryl 3-phosphorylcholine, O-deacetyl platelet-activating factor, from leukocytes: chemical ionization mass spectrometry of phospholipids.. Proc Natl Acad Sci U S A 1980 Dec;77(12):7019-23.
        pubmed: 6938950doi: 10.1073/pnas.77.12.7019google scholar: lookup
      2. Takai Y, Kaibuchi K, Matsubara T, Nishizuka Y. Inhibitory action of guanosine 3', 5'-monophosphate on thrombin-induced phosphatidylinositol turnover and protein phosphorylation in human platelets.. Biochem Biophys Res Commun 1981 Jul 16;101(1):61-7.
        pubmed: 6269550doi: 10.1016/s0006-291x(81)80010-1google scholar: lookup
      3. Serhan C, Anderson P, Goodman E, Dunham P, Weissmann G. Phosphatidate and oxidized fatty acids are calcium ionophores. Studies employing arsenazo III in liposomes.. J Biol Chem 1981 Mar 25;256(6):2736-41.
        pubmed: 6782095
      4. Sheetz MP, Febbroriello P, Koppel DE. Triphosphoinositide increases glycoprotein lateral mobility in erythrocyte membranes.. Nature 1982 Mar 4;296(5852):91-3.
        pubmed: 6278314doi: 10.1038/296091a0google scholar: lookup
      5. Blank ML, Snyder F, Byers LW, Brooks B, Muirhead EE. Antihypertensive activity of an alkyl ether analog of phosphatidylcholine.. Biochem Biophys Res Commun 1979 Oct 29;90(4):1194-200.
        pubmed: 518593doi: 10.1016/0006-291x(79)91163-xgoogle scholar: lookup
      6. Shukla SD, Hanahan DJ. AGEPC (platelet activating factor) induced stimulation of rabbit platelets: effects on phosphatidylinositol, di- and triphosphoinositides and phosphatidic acid metabolism.. Biochem Biophys Res Commun 1982 Jun 15;106(3):697-703.
        pubmed: 6288030doi: 10.1016/0006-291x(82)91767-3google scholar: lookup
      7. Lee TC, Malone B, Blank ML, Snyder F. 1-alkyl-2-acetyl-sn-glycero-3-phosphocholine (platelet-activating factor) stimulates calcium influx in rabbit platelets.. Biochem Biophys Res Commun 1981 Oct 30;102(4):1262-8.
        pubmed: 6797422doi: 10.1016/s0006-291x(81)80147-7google scholar: lookup
      8. Shaw JO, Klusick SJ, Hanahan DJ. Activation of rabbit platelet phospholipase and thromboxane synthesis by 1-O-hexadecyl/octadecyl-2-acetyl-sn-glyceryl-3-phosphorylcholine (platelet activating factor).. Biochim Biophys Acta 1981 Jan 26;663(1):222-9.
        pubmed: 7213765doi: 10.1016/0005-2760(81)90208-3google scholar: lookup
      9. Marcus AJ, Safier LB, Ullman HL, Wong KT, Broekman MJ, Weksler BB, Kaplan KL. Effects of acetyl glyceryl ether phosphorylcholine on human platelet function in vitro.. Blood 1981 Nov;58(5):1027-31.
        pubmed: 6457658
      10. McManus LM, Hanahan DJ, Demopoulos CA, Pinckard RN. Pathobiology of the intravenous infusion of acetyl glyceryl ether phosphorylcholine (AGEPC), a synthetic platelet-activating factor (PAF), in the rabbit.. J Immunol 1980 Jun;124(6):2919-24.
        pubmed: 7373056
      11. Ingraham LM, Coates TD, Allen JM, Higgins CP, Baehner RL, Boxer LA. Metabolic, membrane, and functional responses of human polymorphonuclear leukocytes to platelet-activating factor.. Blood 1982 Jun;59(6):1259-66.
        pubmed: 6282362
      12. Buckley JT, Hawthorne JN. Erythrocyte membrane polyphosphoinositide metabolism and the regulation of calcium binding.. J Biol Chem 1972 Nov 25;247(22):7218-23.
        pubmed: 4344642
      13. Lynch JM, Lotner GZ, Betz SJ, Henson PM. The release of a platelet-activating factor by stimulated rabbit neutrophils.. J Immunol 1979 Sep;123(3):1219-26.
        pubmed: 469247
      14. Harrison DG, Long C. The calcium content of human erythrocytes.. J Physiol 1968 Dec;199(2):367-81.
        pubmed: 4972779doi: 10.1113/jphysiol.1968.sp008658google scholar: lookup
      15. Vargaftig BB, Lefort J, Chignard M, Benveniste J. Platelet-activating factor induces a platelet-dependent bronchoconstriction unrelated to the formation of prostaglandin derivatives.. Eur J Pharmacol 1980 Jul 25;65(2-3):185-92.
        pubmed: 6995139doi: 10.1016/0014-2999(80)90391-xgoogle scholar: lookup
      16. Lapetina EG, Billah MM, Cuatrecasas P. The phosphatidylinositol cycle and the regulation of arachidonic acid production.. Nature 1981 Jul 23;292(5821):367-9.
        pubmed: 6265791doi: 10.1038/292367a0google scholar: lookup
      17. Agranoff BW, Murthy P, Seguin EB. Thrombin-induced phosphodiesteratic cleavage of phosphatidylinositol bisphosphate in human platelets.. J Biol Chem 1983 Feb 25;258(4):2076-8.
        pubmed: 6296123
      18. Owen NE, Le Breton GC. Ca2+ mobilization in blood platelets as visualized by chlortetracycline fluorescence.. Am J Physiol 1981 Oct;241(4):H613-9.
        pubmed: 6274207doi: 10.1152/ajpheart.1981.241.4.H613google scholar: lookup
      19. Goetzl EJ, Derian CK, Tauber AI, Valone FH. Novel effects of 1-O-hexadecyl-2-acyl-sn-glycero-3-phosphorycholine mediators on human leukocyte function: delineation of the specific roles of the acyl substituents.. Biochem Biophys Res Commun 1980 Jun 16;94(3):881-8.
        pubmed: 7396938doi: 10.1016/0006-291x(80)91317-0google scholar: lookup
      20. Lloyd JV, Mustard JF. Changes in 32P-content of phosphatidic acid and the phosphoinositides of rabbit platelets during aggregation induced by collagen or thrombin.. Br J Haematol 1974 Feb;26(2):243-53.
        pubmed: 4367705doi: 10.1111/j.1365-2141.1974.tb00469.xgoogle scholar: lookup
      21. Gerrard JM, Butler AM, Peterson DA, White JG. Phosphatidic acid releases calcium from a platelet membrane fraction in vitro.. Prostaglandins Med 1978 Nov;1(5):387-96.
        pubmed: 103107doi: 10.1016/0161-4630(78)90125-8google scholar: lookup
      22. Kirk CJ, Creba JA, Downes CP, Michell RH. Hormone-stimulated metabolism of inositol lipids and its relationship to hepatic receptor function.. Biochem Soc Trans 1981 Oct;9(5):377-9.
        pubmed: 6269920doi: 10.1042/bst0090377google scholar: lookup
      23. Billah MM, Lapetina EG. Rapid decrease of phosphatidylinositol 4,5-bisphosphate in thrombin-stimulated platelets.. J Biol Chem 1982 Nov 10;257(21):12705-8.
        pubmed: 6290478
      24. Cazenave JP, Benveniste J, Mustard JF. Aggregation of rabbit platelets by platelet-activating factor is independent of the release reaction and the arachidonate pathway and inhibited by membrane-active drugs.. Lab Invest 1979 Sep;41(3):275-85.
        pubmed: 112332
      25. McManus LM, Hanahan DJ, Pinckard RN. Human platelet stimulation by acetyl glyceryl ether phosphorylcholine.. J Clin Invest 1981 Mar;67(3):903-6.
        pubmed: 7204562doi: 10.1172/jci110108google scholar: lookup
      26. Dawson RM. 'Phosphatido-peptide'-like complexes formed by the interaction of calcium triphosphoinositide with protein.. Biochem J 1965 Oct;97(1):134-8.
        pubmed: 16749093doi: 10.1042/bj0970134google scholar: lookup
      27. Billah MM, Lapetina EG. Evidence for multiple metabolic pools of phosphatidylinositol in stimulated platelets.. J Biol Chem 1982 Oct 25;257(20):11856-9.
        pubmed: 6811589
      28. Feinstein MB. Release of intracellular membrane-bound calcium precedes the onset of stimulus-induced exocytosis in platelets.. Biochem Biophys Res Commun 1980 Mar 28;93(2):593-600.
        pubmed: 6992773doi: 10.1016/0006-291x(80)91119-5google scholar: lookup
      29. O'Flaherty JT, Wykle RL, Miller CH, Lewis JC, Waite M, Bass DA, McCall CE, DeChatelet LR. 1-O-Alkyl-sn-glyceryl-3-phosphorylcholines: a novel class of neutrophil stimulants.. Am J Pathol 1981 Apr;103(1):70-8.
        pubmed: 7223864
      30. Hanahan DJ, Demopoulos CA, Liehr J, Pinckard RN. Identification of platelet activating factor isolated from rabbit basophils as acetyl glyceryl ether phosphorylcholine.. J Biol Chem 1980 Jun 25;255(12):5514-6.
        pubmed: 7380824
      31. Hendrickson HS, Reinertsen JL. Comparison of metal-binding properties of trans-1,2-cyclohexanediol diphosphate and deacylated phosphoinositides.. Biochemistry 1969 Dec;8(12):4855-8.
        pubmed: 4312456doi: 10.1021/bi00840a031google scholar: lookup
      32. Weiss SJ, McKinney JS, Putney JW Jr. Receptor-mediated net breakdown of phosphatidylinositol 4,5-bisphosphate in parotid acinar cells.. Biochem J 1982 Sep 15;206(3):555-60.
        pubmed: 6184051doi: 10.1042/bj2060555google scholar: lookup
      33. Lapetina EG. Platelet-activating factor stimulates the phosphatidylinositol cycle. Appearance of phosphatidic acid is associated with the release of serotonin in horse platelets.. J Biol Chem 1982 Jul 10;257(13):7314-7.
        pubmed: 7045103
      34. Billah MM, Lapetina EG. Formation of lysophosphatidylinositol in platelets stimulated with thrombin or ionophore A23187.. J Biol Chem 1982 May 10;257(9):5196-200.
        pubmed: 6802848
      35. Benveniste J, Henson PM, Cochrane CG. Leukocyte-dependent histamine release from rabbit platelets. The role of IgE, basophils, and a platelet-activating factor.. J Exp Med 1972 Dec 1;136(6):1356-77.
        pubmed: 4118412doi: 10.1084/jem.136.6.1356google scholar: lookup

      Citations

      This article has been cited 20 times.
      1. Scherer GF, Martiny-Baron G, Stoffel B. A new set of regulatory molecules in plants: A plant phospholipid similar to platelet-activating factor stimulates protein kinase and proton-translocating ATPase in membrane vesicles. Planta 1988 Aug;175(2):241-53.
        doi: 10.1007/BF00392434pubmed: 24221719google scholar: lookup
      2. Chao W, Olson MS. Platelet-activating factor: receptors and signal transduction. Biochem J 1993 Jun 15;292 ( Pt 3)(Pt 3):617-29.
        doi: 10.1042/bj2920617pubmed: 8391253google scholar: lookup
      3. Lapetina EG, Watson SP, Cuatrecasas P. myo-Inositol 1,4,5-trisphosphate stimulates protein phosphorylation in saponin-permeabilized human platelets. Proc Natl Acad Sci U S A 1984 Dec;81(23):7431-5.
        doi: 10.1073/pnas.81.23.7431pubmed: 6438636google scholar: lookup
      4. Godfrey PP, Putney JW Jr. Receptor-mediated metabolism of the phosphoinositides and phosphatidic acid in rat lacrimal acinar cells. Biochem J 1984 Feb 15;218(1):187-95.
        doi: 10.1042/bj2180187pubmed: 6324749google scholar: lookup
      5. Downes CP, Wusteman MM. Breakdown of polyphosphoinositides and not phosphatidylinositol accounts for muscarinic agonist-stimulated inositol phospholipid metabolism in rat parotid glands. Biochem J 1983 Dec 15;216(3):633-40.
        doi: 10.1042/bj2160633pubmed: 6320795google scholar: lookup
      6. Rittenhouse SE. Human platelets contain phospholipase C that hydrolyzes polyphosphoinositides. Proc Natl Acad Sci U S A 1983 Sep;80(17):5417-20.
        doi: 10.1073/pnas.80.17.5417pubmed: 6310576google scholar: lookup
      7. Rink TJ, Sanchez A. Effects of prostaglandin I2 and forskolin on the secretion from platelets evoked at basal concentrations of cytoplasmic free calcium by thrombin, collagen, phorbol ester and exogenous diacylglycerol. Biochem J 1984 Sep 15;222(3):833-6.
        doi: 10.1042/bj2220833pubmed: 6091624google scholar: lookup
      8. Holmsen H, Dangelmaier CA, Rongved S. Tight coupling of thrombin-induced acid hydrolase secretion and phosphatidate synthesis to receptor occupancy in human platelets. Biochem J 1984 Aug 15;222(1):157-67.
        doi: 10.1042/bj2220157pubmed: 6089753google scholar: lookup
      9. Cockcroft S, Baldwin JM, Allan D. The Ca2+-activated polyphosphoinositide phosphodiesterase of human and rabbit neutrophil membranes. Biochem J 1984 Jul 15;221(2):477-82.
        doi: 10.1042/bj2210477pubmed: 6089740google scholar: lookup
      10. Yousufzai SY, Abdel-Latif AA. Effects of platelet-activating factor on the release of arachidonic acid and prostaglandins by rabbit iris smooth muscle. Inhibition by calcium channel antagonists. Biochem J 1985 Jun 15;228(3):697-706.
        doi: 10.1042/bj2280697pubmed: 3927898google scholar: lookup
      11. Conrad GW, Rink TJ. Platelet activating factor raises intracellular calcium ion concentration in macrophages. J Cell Biol 1986 Aug;103(2):439-50.
        doi: 10.1083/jcb.103.2.439pubmed: 3733874google scholar: lookup
      12. Altin JG, Dieter P, Bygrave FL. Evidence that Ca2+ fluxes and respiratory, glycogenolytic and vasoconstrictive effects induced by the action of platelet-activating factor and L-alpha-lysophosphatidylcholine in the perfused rat liver are mediated by products of the cyclo-oxygenase pathway. Biochem J 1987 Jul 1;245(1):145-50.
        doi: 10.1042/bj2450145pubmed: 3117040google scholar: lookup
      13. Levesque JP, Hatzfeld A, Hatzfeld J. Fibrinogen mitogenic effect on hemopoietic cell lines: control via receptor modulation. Proc Natl Acad Sci U S A 1986 Sep;83(17):6494-8.
        doi: 10.1073/pnas.83.17.6494pubmed: 3018735google scholar: lookup
      14. Sekar MC, Hokin LE. The role of phosphoinositides in signal transduction. J Membr Biol 1986;89(3):193-210.
        doi: 10.1007/BF01870664pubmed: 3009821google scholar: lookup
      15. Sasaki T, Hasegawa-Sasaki H. Breakdown of phosphatidylinositol 4,5-bisphosphate in a T-cell leukaemia line stimulated by phytohaemagglutinin is not dependent on Ca2+ mobilization. Biochem J 1985 May 1;227(3):971-9.
        doi: 10.1042/bj2270971pubmed: 2988510google scholar: lookup
      16. Watson SP, Lapetina EG. 1,2-Diacylglycerol and phorbol ester inhibit agonist-induced formation of inositol phosphates in human platelets: possible implications for negative feedback regulation of inositol phospholipid hydrolysis. Proc Natl Acad Sci U S A 1985 May;82(9):2623-6.
        doi: 10.1073/pnas.82.9.2623pubmed: 2986126google scholar: lookup
      17. de Chaffoy de Courcelles D, Roevens P, Van Belle H. Prostaglandin E1 and forskolin antagonize C-kinase activation in the human platelet. Biochem J 1987 May 15;244(1):93-9.
        doi: 10.1042/bj2440093pubmed: 2822002google scholar: lookup
      18. Ishii H, Umeda F, Hashimoto T, Nawata H. Increased intracellular calcium mobilization in platelets from patients with type 2 (non-insulin-dependent) diabetes mellitus. Diabetologia 1991 May;34(5):332-6.
        doi: 10.1007/BF00405005pubmed: 1907585google scholar: lookup
      19. Shukla SD. Inositol phospholipid turnover in PAF transmembrane signalling. Lipids 1991 Dec;26(12):1028-33.
        doi: 10.1007/BF02536496pubmed: 1668102google scholar: lookup
      20. Chao W, Liu H, Hanahan DJ, Olson MS. Protein tyrosine phosphorylation and regulation of the receptor for platelet-activating factor in rat Kupffer cells. Effect of sodium vanadate. Biochem J 1992 Dec 15;288 ( Pt 3)(Pt 3):777-84.
        doi: 10.1042/bj2880777pubmed: 1335232google scholar: lookup
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