Dinucleotides as growth-promoting extracellular mediators. Presence of dinucleoside diphosphates Ap2A, Ap2G, and Gp2G in releasable granules of platelets.
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.
Jankowski
J
J
Medizinische Klinik IV, Universitätsklinikum Benjamin Franklin, Freie Universität Berlin, Berlin 12200, Germany.
Hagemann
J
J
Tepel
M
M
van Der Giet
M
M
Stephan
N
N
Henning
L
L
Gouni-Berthold
I
I
Sachinidis
A
A
Zidek
W
W
Schluter
H
H
Gouni-Berthold
H
H
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
D006133:Growth Substances; D009841:Oligonucleotides; D013917:Thrombin