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Purinergic Pharmacology

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Besides their intracellular metabolic and genetic roles, purine nucleotides and nucleosides constitute important extracellular signaling molecules. Adenosine 5’-triphosphate (ATP) and adenosine, tightly controlled by nucleotidases and transporters, signal through a rich array of purinergic receptors. These ...

Besides their intracellular metabolic and genetic roles, purine nucleotides and nucleosides constitute important extracellular signaling molecules. Adenosine 5’-triphosphate (ATP) and adenosine, tightly controlled by nucleotidases and transporters, signal through a rich array of purinergic receptors. These receptors, which emerged early in evolution, are among the most abundant in living organisms controlling many physiological actions, thus becoming promising therapeutic targets in a wide range of pathological conditions. While P1 receptors are selective for adenosine, a breakdown product of ATP, P2 receptors are activated by purine nucleotides and eventually by pyrimidines. Interestingly, purinergic receptors, both G protein-coupled (i.e. P1 and P2Y) and ligand-gated ion channel (i.e. P2X) receptors, are involved in many neuronal and non-neuronal mechanisms, including pain, immune responses, exocrine and endocrine secretion, platelet aggregation, endothelial-mediated vasodilatation and inflammation, among others.
Purinergic receptors are ubiquitously expressed throughout the body, thus compromising drug specificity and increasing the possibility of side effects upon pharmacological intervention. On the other hand, the extracellular levels of purines may oscillate enormously, thus distinct purinergic receptors responding differently to low and high concentrations of endogenous purines are needed if a particular cell is exposed to the entire purinergic signaling spectra. Therefore, usually the very same cell concurrently expresses different subtypes of P1 and P2 receptors, which allows the integration of purinergic transmission into short- and long-term signaling events. Accordingly, drug selectivity constitutes another important pharmacological issue within the purinergic field. Indeed, the development of potent and selective synthetic agonists and antagonists for purinergic receptors has been the subject of medicinal chemistry research for decades. In addition, allosteric modulators of purinergic receptors have been successfully developed. Interestingly, these compounds allow the manipulation of the endogenous purinergic system in an event-responsive and temporally specific manner, thus offering a unique therapeutic window when compared to orthosteric compounds. Finally, the functioning of the purinergic system could be also manipulated by modulating the metabolism and/or uptake of extracellular purine nucleotides and nucleosides.
Overall, there is no doubt that purinergic pharmacology is growing fast and becoming an attractive field for pharmacotherapeutic development. Therefore, to boost the scientific discussion and to stimulate the continuing efforts to expand the knowledge of the purinergic field, we encourage investigators to contribute original research as well as review articles. Thus, we welcome articles on the following topics (but not restricted to):

- Molecular pharmacology of purinergic receptors.
- Purinergic medicinal chemistry
- Purinergic structural biology
- Pharmacognosy of purines
- Purinergic receptors as targets in neurodegenerative disorders
- Purines in the gut pathology
- Pharmacology of the cardiovascular purinergic system
- Purinergic systems as target in renal disorders
- Purinergic pharmacology in the senses
- Purines in behavioral disorders
- Purines in cancer disease
- Inflammation and purinergic pharmacology
- Purinergic receptors as targets for endocrine disorders


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