title: Dinucleotides as growth-promoting extracellular mediators. Presence of dinucleoside diphosphates Ap2A, Ap2G, and Gp2G in releasable granules of platelets.
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.
authors: Medizinische Klinik IV, Universitätsklinikum Benjamin Franklin, Freie Universität Berlin, Berlin 12200, Germany.
authors: J
authors: J
authors: Jankowski
authors: J
authors: J
authors: Hagemann
authors: M
authors: M
authors: Tepel
authors: M
authors: M
authors: van Der Giet
authors: N
authors: N
authors: Stephan
authors: L
authors: L
authors: Henning
authors: I
authors: I
authors: Gouni-Berthold
authors: A
authors: A
authors: Sachinidis
authors: W
authors: W
authors: Zidek
authors: H
authors: H
authors: Schluter
authors: H
authors: H
authors: Gouni-Berthold
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002853:Chromatography, Liquid / Q000379:methods; D006133:Growth Substances / Q000302:isolation & purification / Q000502:physiology*; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000166:cytology; D009841:Oligonucleotides / Q000302:isolation & purification / Q000378:metabolism*; D015539:Platelet Activation / Q000187:drug effects; D051381:Rats; D011921:Rats, Inbred WKY; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013917:Thrombin / Q000494:pharmacology
chemical_list: D006133:Growth Substances; D009841:Oligonucleotides; D013917:Thrombin