Purinergic regulation: From a risky hypothesis to a triumphant theory

Abstract

With the discovery of the ATP structure in 1929, significant progress was made in understanding the role of nucleosides and nucleotides in the body. One of the most important breakthroughs is associated with the determination of the function of an autacoid in ATP, a participant in purinergic signal transmission. For the first time, this function of ATP was pointed out by Professor Geoffrey Burnstock in 1972. Purinergic signaling activators are extracellular nucleotides including ATP, ADP, UTP, UDP, and adenosine nucleoside. The purinergic signaling pathway begins with the synthesis and intracellular accumulation of nucleotides, and then their release from the cell under various physiological and pathological conditions. In the extracellular spaces, nucleotides are hydrolyzed by various enzymes with the removal of phosphate groups, which leads to the appearance of various regulatory molecules that interact with P1 and P2 purinergic receptors. This ligand-receptor interaction changes the functional state of the target cell. In turn, the expression of purinergic receptors changes depending on the functional state of the cell. The participation of purinergic regulation in the development of many diseases indicates that by changing the concentration of signaling molecules, it is possible to change the course of pathological processes, in particular the activity of inflammation and the direction of immune responses. This article provides a brief review of the literature on the structure of nucleotide and nucleoside autacoids, enzymes involved in their metabolism, specific purinergic receptors.