SIGNAL TRANSDUCTION OF INEFFICIENT ELIMATION OF SMALL STONES FROM THE MIDDLE THIRD OF THE URETER

DOI: https://doi.org/10.29296/24999490-2022-04-07

E.F. Barinov, Kh.V. Grigoryan, Y.Yu. Malinin
State educational organization of higher professional education «M. Gorky Donetsk National Medical University»,
Ilyicha Avenue, 16, Donetsk, 84003, DPR

Аim of the study was to evaluate the activity of receptors that control contraction (α2-adrenergic receptor, purine P2X1 and P2Y receptors, angiotensin AT1 receptor, TxA2 receptor) and relaxation of smooth myocytes (adenosine A2 receptor) during standard lithokinetic therapy (LCT) in patients with localization of small (≤6mm) stones in the middle third of the ureter. Material and methods. The study was prospective and included 17 patients with ineffective elimination of small stones during 9 days of standard LCT. Analysis of the receptors activity that modulate ureteral motility was performed in vitro on a platelet suspension. 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. At the stage of hospitalization of patients (before the start of LCT), hyperreactivity of the angiotensin AT1 receptor, purine P2X1 and P2Y receptors, α2-adrenergic receptor, TxA2 receptor and adenosine A2 receptor was revealed. This reflects the presence of signal transduction in nephrolithiasis, which is capable of modulating the contraction and relaxation of smooth muscle tissue of the ureter. After 3 days of LCT, intracellular signaling is characterized by hyperreactivity of the AT1 receptor and normoreactivity of the α2 adrenoreceptor, P2X1 receptor, and P2Y receptors; The revealed relationship of the AT1 receptor with the α2-adrenergic receptor and P2X1 receptors does not provide an increase in ureteral motility. After 6 days of LCT, insufficient contractile activity of the muscular layer may be associated with limited activation of the α2-adrenergic receptor, as well as a weak interaction of the AT1 receptor with purine P2X1 and P2Y receptors. After 9 days of LCT, the violation of the traffic of small stones in the ureter is associated with desensitization of the α2-adrenoreceptor and P2X1 receptor, as well as hyperreactivity and interaction of the AT1 receptor and P2Y receptors. Conclusion. The variability of intracellular signaling in case of ineffective elimination of small calculi from the middle third ureter is determined by the influence of nephrolithiasis pathogenesis factors and the low specificity of LCT in relation to the processes of contraction and relaxation of smooth muscle tissue.
Keywords: 
ephrolithiasis, lithokinetic therapy, small stone traffic, ureteral muscularis, intracellular signaling pathways
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