From purines to purinergic signalling: molecular functions and human diseases

Abstract

Purines and their derivatives, most notably adenosine and ATP, are the key molecules controlling intracellular energy homoeostasis and nucleotide synthesis. Besides, these purines support, as chemical messengers, purinergic transmission throughout tissues and species. Purines act as endogenous ligands that bind to and activate plasmalemmal purinoceptors, which mediate extracellular communication referred to as “purinergic signalling”. Purinergic signalling is cross-linked with other transmitter networks to coordinate numerous aspects of cell behaviour such as proliferation, differentiation, migration, apoptosis and other physiological processes critical for the proper function of organisms. Pathological deregulation of purinergic signalling contributes to various diseases including neurodegeneration, rheumatic immune diseases, inflammation, and cancer. Particularly, gout is one of the most prevalent purine-related disease caused by purine metabolism disorder and consequent hyperuricemia. Compelling evidence indicates that purinoceptors are potential therapeutic targets, with specific purinergic agonists and antagonists demonstrating prominent therapeutic potential. Furthermore, dietary and herbal interventions help to restore and balance purine metabolism, thus addressing the importance of a healthy lifestyle in the prevention and relief of human disorders. Profound understanding of molecular mechanisms of purinergic signalling provides new and exciting insights into the treatment of human diseases.

ATP and Adenosine in the Retina and Retinal Diseases

“…For instance, many drugs targeting purine metabolism or purinergic signaling have been developed. The US FDA database shows that several approved purinergic signaling target-related drugs, including adenosine and caffeine citrate injection, are mainly used in the cardiovascular system (Huang et al, 2021). In addition, Gefapixant (AF-219) (P2X3R antagonist) is used for the chronic cough.…”

“…Purines and their derivatives, most notably adenosine and ATP, are the key molecules controlling intracellular energy homoeostasis and nucleotide synthesis (Huang et al, 2021). High concentrations of ATP are present within cells and ATP is released into the extracellular milieu during cellular damage or death.…”

Resveratrol and Quercetin as Regulators of Inflammatory and Purinergic Receptors to Attenuate Liver Damage Associated to Metabolic Syndrome

“…After an inflammatory signal, adenosine 5 -triphosphate (ATP) is released into the extracellular space. ATP is known for its important role in intracellular cell metabolic pathways; however, this nucleotide can also act as a danger signal on the purinergic receptors (P2X or P2Y) which are diffusely expressed in various organs including the liver [13]. These receptors are essential regulators of physiological functions and serve as danger signals that trigger inflammation after injury [14].…”

“…These receptors are essential regulators of physiological functions and serve as danger signals that trigger inflammation after injury [14]. Purinergic signaling, by P2Y, interacts with other signaling molecules to form a complex network, regulating numerous cellular processes including phagocytosis, chemotaxis, cytokine production, proliferation, differentiation, and death [13,15]. P2Y2 receptors are also associated with fat accumulation, hepatic steatosis, IR, metabolic complications, and inflammation [16,17].…”

Purinergic ATP triggers moxibustion-induced local anti-nociceptive effect on inflammatory pain model

“…Since purinergic signalling was proposed by Prof. Geoffrey Burnstock (1929Burnstock ( -2020 in 1972 [1], it has been recognized as one of promising drug target [2][3][4][5][6][7][8]. Purinergic signalling is also hypothesized and has been found to get involved in the mechanism of acupuncture therapy (i.e., the acupuncture family procedure, including needle therapy, moxibustion therapy, cupping therapy, etc.)…”