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EFFICIENCY OF LITHOKINETIC THERAPY IN NEPHROLITHIASIS: THE ROLE OF COMPENSATORY MECHANISMS PROVIDING TRAFFIC OF MEDIUM-SIZED STONES IN THE URETER

DOI: https://doi.org/10.29296/25877305-2022-12-12
Issue: 
12
Year: 
2022

Professor E. Barinov, MD; Yu. Malinin, Candidate of Medical Sciences;
Kh. Grigoryan, Candidate of Medical Sciences
M. Gorky Donetsk National Medical University, Donetsk, Donetsk People's Republic

Аim of the study was to analyze the activity of receptors that control contraction (α2-adrenergic receptor, purine P2X1- and P2Y receptors, angiotensin AT1 receptor, TxA2 receptor) and relaxation of smooth muscle cells (adenosine A2 receptor) while maintaining and blocking α1A-adrenoreceptor during lithokinetic therapy (LCT) in patients with medium-sized calculi in the ureter. Material and methods. The study was prospective and included 30 patients with effective (Group 1) and ineffective (Group 2) elimination of stones 11–13 mm in size. Differences in LCT related to the appointment of an α1A-adrenergic receptor antagonist. Analysis of the functional activity of receptors involved in the regulation of ureteral motility was performed in vitro on platelet suspensions. The following agonists were used: ATP, ADP, adenosine, epinephrine, angiotensin-2 (Sigma-Aldrich Chemie GmbH, Germany). Platelet aggregation was assessed by the turbidimetric method on a ChronoLog analyzer (USA). Results. Before LCT, the reactivity of receptors was revealed, signaling pathways of which can modulate the violation of the traffic medium-sized calculi in the ureter. Effective elimination of calculi after 7–9 days of LCT with the functioning of the α1A-adrenergic receptor was reproduced in a cohort of patients with the presence of: hyperreactivity of the A2A receptor, P2X1 receptor and hyporeactivity of the α2-adrenoreceptor, TxA2 receptor. Ineffective elimination of calculi in LCT with an α1A-adrenoreceptor antagonist is associated with impaired intracellular signaling due to excessive activation of the α2-adrenoreceptor, P2X1 receptor, P2Y receptors, AT1 receptor, TxA2 receptor and desensitization of the adenosine A2A receptor. The hyperreactivity of the Gq-protein-coupled receptor system (GPCR system) can neutralize the effect of the administration α1A-adrenergic receptor antagonist, since the «crosstalk» of intracellular signaling is reproduced, resulting in the preservation of an excess level of intracellular Ca2+ in smooth muscle cells. Conclusion. In vitro analysis of intracellular signaling, which regulates the entry of Ca2+ into the cell upon activation of the GPCR system and the removal of excess Ca2+ through the adenosinergic system, makes it possible to clarify the mechanisms that maintain the balance of relaxation and contraction of smooth muscle cells during the traffic of medium-sized calculi.

Keywords: 
nephrolithiasis
lithokinetic therapy
medium calculus traffic
platelet suspension
G protein-coupled receptors (GPCR system)
adenosinergic system
intracellular signaling pathways



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