We report the identification of a hitherto unknown nucleotide that is present in micromolar concentrations in the erythrocytes of healthy subjects and accumulates at levels comparable with the ATP concentration in erythrocytes of patients with chronic renal failure. The unknown nucleotide was isolated and identified by liquid chromatography with UV and tandem mass detection, . We suggest that 4PYTP formation in the erythrocytes is a hitherto unknown process aimed at sequestering potentially toxic 4PYR in a form that could be safely transported and subsequently released and excreted during passage of erythrocytes through the kidney.
Secretion of parathormone (PTH), the main parathyroid hormone, which is under the control of the calcium sensing receptor, might be inhibited by calcimimetics and stimulated by calcilytics. Parathyroid glands also secrete parathyroid hypertensive factor. Recently, it was shown that calcimimetic NPS R-568 induced decreased blood pressure in spontaneously hypertensive rats (SHR) in the presence of parathyroid glands. Therefore, the aim of this study was to determine whether administration of the calcilytic NPS 2143 provoked an increase of mean arterial blood pressure (MAP) in normotensive rats. We used male Wistar rats anaesthetized with thiopental. Clearance experiments were performed and the effect of bolus, 1 mg/kg body weight i.v. of NPS 2143 on MAP in the presence and absence of thyroparathyroidectomy (TPTX) was monitored continuously. Calcilytic properties of NPS 2143 were confirmed directly by a significant (P!0$05) increase of plasma PTH concentration, and indirectly by a rise of plasma Ca 2C concentration and urinary fractional phosphate excretion (FE Pi). NPS 2143 administration markedly (P!0$05) increased MAP, calculated as the difference (D) in MAP between sequential measurements and the time of bolus injection of calcilytic. The observed increase of blood pressure in the NPS 2143 group was also significant (P!0$05) compared with the control group. Performance of TPTX prevented the hypertensive effect of NPS 2143. We conclude that NPS 2143 is responsible for increased blood pressure in rats in the presence of parathyroid glands.
We recently discovered new nucleotides (4-pyridone-3-carboxamide-1-beta -D-ribonucleoside phosphates) in human erythrocytes. To establish the precursor compound and pathways of nucleotide derivative formation and breakdown, human erythrocytes were incubated for 3 hours with 0.3 mM 4-pyridone-3-carboxamide-1-beta-D-ribonucleoside (4PYR) and erythrocyte concentrations of 4PYR and adenine nucleotides were followed. 4PYR triphosphate increased from 16.1 +/- 0.6 micro M to 74.9 +/- 9.17 and 4PYR monophosphate increased from 5 micro M to 254.7 +/- 13.9 micro M. Conversely, incubation with 0.3 mM 4-pyridone-3-carboxamide (4PY) did not lead to additional 4PYR nucleotide formation. 4PYR nucleotides were catabolized to 4PYR. We conclude that 4PYR nucleotides are formed in erythrocytes by nucleoside kinase-mediated 4PYR phosphorylation and catabolized by 5'nucleotidase-mediated dephosphorylation.
In the work presented, thiol- and COOH-terminated dipyrromethene derivatives have been applied for gold electrode modification. Dipyrromethene deposited onto a solid support, after binding Cu2+, can act as a redox active monolayer. The complexation of Cu(II) ions has been performed on the surface of gold electrodes modified with dipyrromethene. The characterization of dipyrromethene-Cu(II) self-assembled monolayers (SAMs) has been done by cyclic voltammetry (CV), wettability contact angle measurements, and atomic force microscopy (AFM). The new electroactive monolayer could be applied for the immobilization of proteins and ssDNA or for electrochemical anion sensing without redox markers in the solution.
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