Dinucleotides as growth-promoting extracellular mediators. Presence of dinucleoside diphosphates Ap2A, Ap2G, and Gp2G in releasable granules of platelets

J Biol Chem. 2001 Mar 23;276(12):8904-9. doi: 10.1074/jbc.M009527200. Epub 2000 Dec 13.

Abstract

Dinucleoside diphosphates, Ap(2)A, Ap(2)G, and Gp(2)G represent a new class of growth-promoting extracellular mediators, which are released from granules after activation of platelets. The presence of theses substances was shown after purification from a platelet concentrate. The substances were identified by UV spectrometry, retention time comparison with authentic substances, matrix-assisted laser desorption/ionization mass spectrometry, post-source-decay matrix-assisted laser desorption/ionization mass spectrometry, and enzymatic analysis. Ap(2)A, Ap(2)G, and Gp(2)G have growth-stimulating effects on vascular smooth muscle cells in nanomolar concentrations as shown by [(3)H]thymidine incorporation measurements. The calculated EC(50) (log m; mean +/- S.E.) values were -6.07 +/- 0.14 for Ap(2)A, -6.27 +/- 0.25 for Ap(2)G, and -6.91 +/- 0.44 for Gp(2)G. At least 61.5 +/- 4.3% of the dinucleoside polyphosphates are released by platelet activation. The intraplatelet concentrations suggest that, in the close environment of a platelet thrombus, similar dinucleoside polyphosphate concentrations can be found as in platelets. Intraplatelet concentration can be estimated in the range of 1/20 to 1/100 of the concentration of ATP. In conclusion, Ap(2)A, Ap(2)G, and Gp(2)G derived from releasable granules of human platelets may play a regulatory role in vascular smooth muscle growth as growth-promoting mediators.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Platelets / metabolism
  • Cell Division / drug effects
  • Chromatography, Liquid / methods
  • Growth Substances / isolation & purification
  • Growth Substances / physiology*
  • Humans
  • Muscle, Smooth, Vascular / cytology
  • Oligonucleotides / isolation & purification
  • Oligonucleotides / metabolism*
  • Platelet Activation / drug effects
  • Rats
  • Rats, Inbred WKY
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
  • Thrombin / pharmacology

Substances

  • Growth Substances
  • Oligonucleotides
  • Thrombin