Objective. Evaluation of the molecular mechanisms that modulate the rapid elimination of small (≤6 mm) stones in the middle third of the ureter.
Material and methods. The prospective study included 21 patients with rapid (within 24–72 hours) elimination of stones from the middle third of the ureter against the background of standard lithokinetic therapy. Analysis of the functional activity of receptors that modulate ureteral motility was performed on a platelet suspension in vitro. 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. During the elimination of stones in the first 24 hours of lithokinetic therapy, hyperreactivity of the α2-adrenergic, angiotensin AT1, purine P2Y and P2X1 receptors was revealed. This fact confirms the possibility of enhancing the contractile activity of the ureter through the sympathetic-adrenal (SAS) and renin-angiotensin systems (RAS), as well as the local myogenic mechanism associated with an increase in the extracellular ADP level. Delayed for 48–72 hour elimination of stones was characterized by modulation of ureteral motility through the α2-adrenoreceptor due to activation of the CAS and the ATP-induced purine P2X1 receptor. The revealed P2X1 receptor hyperreactivity may be associated with the need to increase the force of contraction of the smooth muscle tissue of the ureter in conditions of limited RAS activity and persistent urinary tract ischemia. A necessary condition for the elimination of small stones was the maintenance of the basal level of relaxation of the ureteral muscularis which was achieved by maintaining the adenosine A2A receptor normoreactivity.
Conclusion. The variability in the timing of rapid elimination of small stones during lithokinetic therapy is determined by the individual characteristics of the formation and regulation of compensatory mechanisms in the process of nephrolithiasis, the purpose of which is to optimize the processes of contraction and relaxation of the ureteral muscularis.

Keywords: intracellular signaling pathways, ureteral muscularis, small stone elimination, lithokinetic therapy, nephrolithiasis