gms | German Medical Science

Diadenosine polyphosphates were demonstrated to be involved in the control of vascular tone as well as the growth of vascular smooth muscle cells and hence, possibly, in atherogenesis. In this study we investigated the question, if diadenosine polyphosphates are present in human plasma and if a potenial source can be identified, which may release diadenosine polyphosphates into the circulation.

Plasma diadenosine polyphosphates (ApnA with n=3-6) were purified to homogeneity by affinity-, anion exchange- and reversed phase-chromatography from deproteinized human plasma. Analysis of the homogeneous fractions with matrix-assisted laser desorption/ionisation mass spectrometry (MALDI-MS) revealed molecular masses ([M+H]+) of 757, 837, 917 and 997 Da. Comparison of the post-source-decay (PSD)-MALDI mass spectra of these fractions with those of authentic diadenosine polyphosphates revealed that these isolated substances were identical to Ap3A, Ap4A, Ap5A and Ap6A. Enzymatic analysis showed an interconnection of the phosphate groups with the adenosines in the 5´-positions of the ribose moieties.

The mean plasma diadenosine polyphosphate concentrations (mean ± SEM) in cubital veins of normotensive subjects amounted to 0.89 ± 0.59 for Ap3A, 0.72 ± 0.72 for Ap4A , 0.33 ± 0.24 for Ap5A, 0.18 ± 0.18 for Ap6A (µmol l-1). Cubital venous plasma diadenosine polyphosphate concentrations from normotensives did not differ significantly from those in the hypertensive patients studied. There was no significant difference between arterial and venous diadenosine polyphosphate plasma concentrations in 5 hemodialysis patients, making a significant degradation by capillary endothelial cells unlikely.

The ApnA (with n=3-6) plasma concentrations in adrenal veins were significantly higher than the plasma concentrations in both infrarenal and suprarenal vena cava: adrenal veins: Ap3A: 4.05 ± 1.63; Ap4A: 6.18 ± 2.08; Ap5A: 0.53 ± 0.28; Ap6A: 0.59 ± 0.31; infrarenal vena cava: Ap3A: 1.25 ± 0.66; Ap4A: 0.91 ± 0.54; Ap5A: 0.25 ± 0.12; Ap6A: 0.11 ± 0.06; suprarenal vena cava: Ap3A: 1.40 ± 0.91; Ap4A: 1.84 ± 1.20; Ap5A: 0.33 ± 0.13; Ap6A: 0.11 ± 0.07 (µmol L-1; mean ± SEM; each p<0.05 (concentration of adrenal veins vs. infrarenal and suprarenal veins respectively).

In conclusion, the presence of diadenosine polyphosphates in physiologically relevant concentrations in human plasma were demonstrated. Since in adrenal venous plasma significantly higher diadenosine polyphosphate concentrations were measured than in plasma from the infrarenal and suprarenal vena cava, it can be assumed that in humans, beside platelets, the adrenal medulla may be a source of plasma diadenosine polyphosphates.