P2-receptors of the urinary bladder as potential targets for novel drugs

Abstract

Purinergic P2 receptors, the basic endogenous agonist of which is adenosine triphosphoric acid (ATP), are widely spread in the organs and tissues of human and animals including urogenitary system. Physiologically, in the peripheral nervous system the role of P2 receptors in most cases is not leading, they only complement or modulate the action of main neuromediators (acetylcholine, norepinephrine). But in pathology the role of P2 receptors significantly increases and often takes the lead in the pathogenesis of one or another disease. In particular, it was determined that purinergic component of contractile bladder response increases from 2-5% in normal state to 40% in some pathological processes (such as interstitial cystitis, neurogenic bladder, urinary obstruction). In the bladder of experimental animals different subtypes of P2 receptors were revealed, their functional role was established in normal conditions and models of pathological processes. Certain subtypes of P2 receptors were also detected in the human bladder, including in some urinary tract diseases. The level of ATP in patients’ urine was established to significantly increase in lower urinary tract obstruction that holds certain promise for the diagnosis of these diseases. Variety and large representation of P2 receptors in lower urinary tract make them attractive as potential targets for novel drugs. On this evidence, evaluation of effect of P2 receptor agonists and antagonists as well as medications affecting the metabolism of endogenous nucleotides and nucleosides, is one of promising direction for the search for new urological drugs.