Catabolism of Ap4A and Ap3A in whole blood. The dinucleotides are long-lived signal molecules in the blood ending up as intracellular ATP in the erythrocytes.
Adenosine(5')tetraphospho(5')adenosine (Ap4A) and adenosine(5')triphospho(5')adenosine (Ap3A) are stored in large amounts in human platelets. After activation of the platelets both dinucleotides are released into the extracellular milieu where they play a role in the modulation of platelet aggregation and also in the regulation of the vasotone. It has recently been shown that the dinucleotides are degraded by enzymes present in the plasma [Lüthje, J. & Ogilvie, A. (1987) Eur. J. Biochem. 169, 385-388]. The further metabolism as well as the role of blood cells has not been established. The dinucleotides were first degraded by plasma phosphodiesterases yielding ATP (ADP) plus AMP as products which were then metabolized to adenosine and inosine. The nucleosides did not accumulate but were very rapidly salvaged by erythrocytes yielding intracellular ATP as the main product. Although lysates of platelets, leucocytes and red blood cells contained large amounts of Ap3A-degrading and Ap4A-degrading activities, these activities were not detectable in suspensions of intact cells suggesting the lack of dinucleotide-hydrolyzing ectoenzymes. Compared to ATP, which is rapidly degraded by ectoenzymes present on blood cells, the half-life of Ap4A was two to three times longer. Since the dinucleotides are secreted together with ADP and ATP from the platelets, we tested the influence of ATP on the rate of degradation of Ap4A. ATP at concentrations present during platelet aggregation strongly inhibited the degradation of Ap4A in whole blood. It is suggested that in vivo the dinucleotides are protected from degradation immediately after their release. They may thus survive for rather long times and may act as signals even at sites far away from the platelet aggregate.
Lüthje
J
J
Institut für Biochemie, Friedrich-Alexander-Universität Erlangen-Nürnberg, Federal Republic of Germany.
Ogilvie
A
A
D000227:Adenine Nucleotides / Q000097:blood*; D000255:Adenosine Triphosphate / Q000097:blood*; D001792:Blood Platelets / Q000378:metabolism; D001826:Body Fluids / Q000378:metabolism*; D015226:Dinucleoside Phosphates; D004912:Erythrocytes / Q000378:metabolism*; D006207:Half-Life; D006801:Humans; D007424:Intracellular Fluid / Q000378:metabolism*; D010949:Plasma / Q000378:metabolism
D000227:Adenine Nucleotides; D015226:Dinucleoside Phosphates; C020733:diadenosine tetraphosphate; C011440:diadenosine triphosphate; D000255:Adenosine Triphosphate