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1
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The relationship between constitutive ATP release and its extracellular metabolism in isolated rat kidney glomeruli

100%
Karczewska J., Martyniec L., Dzierzko G., Stepinski J., Angielski S.
Journal of Physiology and Pharmacology
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2007
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tom 58
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nr 2
ATP and adenosine are important extracellular regulators of glomerular functions. In this study, ATP release from glomeruli suspension and its extracellular metabolism were investigated. Basal extraglomerular ATP concentration (1nM) increased several fold during inhibition of ecto-ATPase activity, reflecting the basal ATP release rate. Mechanical perturbation increased the amounts of ATP released from glomeruli. ATP added to glomeruli was almost completely degraded within 20 minutes. In that time, AMP was the main product of extracellular ATP metabolism. Significant accumulation of AMP was observed after 5 min (194 ±16 µM) and 20 min (271 ±11 µM), whereas at the same time concentration of adenosine was only 10 µM. A competitive inhibitor of ecto-5-nucleotidase alpha-ß-methylene-ADP (AOPCP), decreased extraglomerular ATP and adenosine concentration by 80% and 50%, respectively. Similarly, AMP (100 µM) also markedly reduced extraglomerular ATP accumulation, whereas IMP, its deamination product, was not effective. P1, P5-diadenosine pentaphosphate (Ap5A) - an inhibitor of ecto-adenylate kinase prevented significantly the disappearance of ATP from extraglomerular media caused by AMP. These findings demonstrate that the decrease in extracellular ATP concentration observed after addition of AOPCP or AMP is caused by the presence of ecto-adenylate kinase activity in the glomeruli. The enzyme catalyses reversible reaction 2ADPATP+AMP, and a rise in the AMP concentration can lead to fall in ATP level. The present study provides evidence the extraglomerular accumulation of ATP reflects both release of ATP from glomeruli cells and its metabolism by ecto-enzymes. Our data suggest that AMP, produced from ATP in the Bowman's capsular space, might plays a dual role as a substrate for ecto-adenylate kinase and ecto-nucleotidase reactions being responsible for the regulation of intracapsular ATP and adenosine concentration. We conclude that AMP degrading and converting ecto-enzymes effectively determine the balance between ATP and adenosine concentration and thus the activation of P2 and/or adenosine receptors.
2
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Co-operation between particulate and soluble guanylyl cyclase systems in the rat renal glomeruli

84%
Stepinski J., Wendt U., Lewko B., Angielski S.
Journal of Physiology and Pharmacology
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2000
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tom 51
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nr 3
3
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Pathways of glomerular toxicity of cyclosporine-A: an "in vitro" study

84%
Castello L., Sainaghi P. P., Bergamasco L., Letizia C., Bartoli E.
Journal of Physiology and Pharmacology
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2005
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tom 56
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nr 4
Background/Aims. Knowledge of renal toxicity of cyclosporine-A (CyA) is clouded by multiple effects on different glomerular and tubular cells and on kidney and systemic hemodynamics. To focus on glomerular action of CyA we used glomeruli isolated in vitro, with the aim of dissecting the effects on recruitment of glomerular vasoconstricting systems, like endothelin-1 (ET) and angiotensins (AI and AII). Methods. We studied the pathways of CyA damage on pig glomeruli isolated in vitro with the technique of sieving through mesh filters of different sizes, and incubated in an appropriate culture medium. The supernatant was sampled at different time intervals to measure ET, AI and AII concentrations upon addition of ET 10-12 or CyA 4·10-7 M, with or without either selective endothelin receptor A (ETA) or B (ETB), or unselective ETA-ETB receptor inhibitors. Results. CyA increased ET concentration (from 9.7±0.3 to 11.4±0.4 pg·ml-1, p<0.002), and the added ET released AI in the medium (from 26.6±4.7 to 39.1±4.6 pg·ml-1, p<0.05) when ETB receptors were blocked. In contrast, CyA stimulated angiotensins release independent of ET receptors blockade, hence, irrespective of ET concentration in the medium, from 26.6±4.7 to 38.0±2.1 pg·ml-1 for AI, p<0.05, and from 12.3±1.0 to 14.8±0.9 pg·ml-1 for AII, p<0.05. Conclusion. CyA releases ET and angiotensins independently by a direct action. Glomerular CyA toxicity might be mediated by recruitment of vasoconstricting peptides and modulated by relative ETA and ETB receptor occupancy.
4
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Bidirectional action of extracellular ATP on intracapillary volume of isolated rat renal glomeruli

84%
Jankowski M., Szczepanska-Konkel M., Kalinowski L., Angielski S.
Journal of Physiology and Pharmacology
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2000
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tom 51
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nr 3
5

Ultrastructural changes of the filtration barrier during mouse nephron development

84%
Okroj W., Bartel H.
Folia Morphologica
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1998
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tom 57
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nr 2
6
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Effect of cAMP analogues on glomerular inulin space of isolated rats renal glomeruli

84%
Van Bemmelen M. X. P., Szczepanska-Konkel M., Jastorff B., Jankowski M., Angielski S.
Journal of Physiology and Pharmacology
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2005
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tom 56
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nr 1
Cyclic AMP has been generally recognised as activator of cAMP-dependent protein kinases. However, there is little evidence about role of cAMP-dependent protein kinase (PKA), in particular izoenzymes PKA-I and PKA-II, in glomeruli contractility. We measured changes of glomerular inulin space (GIS) as a marker of its contractility in the presence of phosphodiesterase resistance cAMP analogues; activators and inhibitors of PKA. Activator of PKA i.e. (Sp) 8-Cl-cAMPS (0.1-100 µM) decreased GIS. (Rp) 8-Cl-cAMPS (0.1-100 µM), inhibitor of PKA, was ineffective but shifted concentration-response curve of (Sp) 8-Cl-cAMPS to right at 50 µM. Specific A site activation by N6-benzoyl-cAMP decreased GIS with maximum at 0.1 µM. Activation of B site by 8-aminobutyloamino-cAMP (0.1-100 µM) had no effect. However, specific activation of both sites on PKA-I or PKA-II by site-selective analogue pairs e.g. 8-aminobutyloamino-cAMP plus 8-piperidino-cAMP or N6-benzoyl-cAMP plus 8-piperidino-cAMP respectively, significantly increased sensitivity of glomeruli to analogues. Our data suggest that activation of PKA-I or PKA-II might have an important role in the regulation of glomerular contractility.
7
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Strong association between fibronectin accumulation and lowered cathepsin B activity in glomeruli of diabetic rats

67%
Wyczalkowska-Tomasik A., Bartolomiejczyk I., Gornicka B., Paczek L.
Journal of Physiology and Pharmacology
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2012
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tom 63
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nr 5
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