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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

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