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Novozhilov A. V. Mindukshev I. V. Korf E. A. Krivchenko A. I. Goncharov N. V. 《Bulletin of experimental biology and medicine》2020,168(4):444-448
Bulletin of Experimental Biology and Medicine - Ammonium, an end-product of catabolism, in low doses can promote adaptation of metabolic pathways in erythrocytes under conditions of extreme... 相似文献
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Sakaev MR Mindukshev IV Lesiovskaia EE Petrishchev NN Krivchenko AI 《Eksperimental'naia i klinicheskaia farmakologiia》2000,63(3):65-69
The effect of purines on the activation and aggregation of thrombocytes in rats and rabbits was studied by the method of small-angle light scattering. The EC50 values of ADP, inducing the activation and aggregation of thrombocytes, reflect the sequence of the agonist action on various receptors: P2X1, 20-40 nM; P2Y1, 90-110 nM; P2YADP, 120-240 nM. It was demonstrated that ADP behaves as partial agonist not only with respect to P2X1 receptors, but with respect to P2Y1 receptors as well. Thrombocytes activated by 20 nM ADP or 100-nM ATP pass into a refracter state in the absence of further stimulation. The reaction halftime is tau 1/2 = 6.0 +/- 0.2 min for the cells activated with ADP and tau 1/2 = 16.5 +/- 0.2 min for ADP. 相似文献
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Shabanova EY Mindukshev IV Malakhovskaya EA Vivulanets EV Petrishchev NN Krivchenko AI 《Bulletin of experimental biology and medicine》2005,140(3):282-284
We found that gestosis is associated with platelet hypersensitivity to ADP. Cell P2X1 receptors exhibited a positive cooperative
response to ADP (EC50=10.88±3.70 nM, Hill constant n=2.59±0.50 rel. units). Cooperative binding of ADP to platelet P2X1 receptors was also observed during incubation of cells
from pregnant women with isosorbide dinitrate.
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Translated from Byulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 140, No. 9, pp. 261–264, September, 2005 相似文献
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I. A. Zhuravin E. F. Derkachev A. K. Dobrylko I. V. Mindukshev A. I. Krivchenko 《Bulletin of experimental biology and medicine》1993,116(1):781-783
Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 116, N
o
7, pp. 19–21, July, 1993 相似文献
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C. Reiss I. Mindukshev V. Bischoff H. Subramanian L. Kehrer A. Friebe J.‐P. Stasch S. Gambaryan U. Walter 《British journal of pharmacology》2015,172(21):5199-5210
Background and Purpose
Stimulation of soluble guanylyl cyclase (sGC) is a valuable therapeutic strategy for the treatment of several cardiovascular diseases. The sGC stimulator riociguat has been approved for the treatment of two forms of pulmonary hypertension. Platelets contain large amounts of sGC and play a key role in the regulation of haemostasis. Therefore, we investigated the effects of riociguat on platelet function.Experimental Approach
The effect of riociguat treatment on human platelet activation and aggregation was investigated. The sGC‐specific effects of riociguat were determined by comparing wild‐type and platelet‐specific sGC‐knockout mice.Key Results
Riociguat induced cGMP synthesis and subsequent PKG activation in human platelets, suggesting that the inhibitory effects are mediated by cGMP signalling. This finding was confirmed when sGC‐knockout platelets were not inhibited by riociguat. In washed human platelets, 100 nM riociguat reduced ADP‐induced GPIIb/IIIa activation, while a 10‐fold higher concentration was required to reduce convulxin‐stimulated GPIIb/IIIa activation. Riociguat inhibited ADP‐induced platelet shape change and aggregation, while ATP‐induced shape change remained unaffected. However, in PRP and whole blood, 50–100 μM riociguat was required to inhibit platelet activation and aggregation. Riociguat in combination with iloprost significantly inhibited platelet aggregation, even in whole blood.Conclusions and Implications
Riociguat inhibits platelet activation in whole blood only at concentrations above 50 μM, while the plasma concentrations in riociguat‐treated patients are 150 to 500 nM. This finding indicates that riociguat treatment does not affect platelet function in patients. Nevertheless, the possibility that riociguat acts synergistically with iloprost to inhibit platelet activation should be considered.Abbreviations
- CTEPH
- chronic thromboembolic pulmonary hypertension
- FDA
- Food and Drug Administration
- LaSca
- low‐angle scattering
- PAH
- pulmonary arterial hypertension
- sGC
- soluble guanylyl cyclase
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