Guanosine-Based Nucleotides, the Sons of a Lesser God in the Purinergic Signal Scenario of Excitable Tissues

Abstract

Purines are nitrogen compounds consisting mainly of a nitrogen base of adenine (ABP) or guanine (GBP) and their derivatives: nucleosides (nitrogen bases plus ribose) and nucleotides (nitrogen bases plus ribose and phosphate). These compounds are very common in nature, especially in a phosphorylated form. There is increasing evidence that purines are involved in the development of different organs such as the heart, skeletal muscle and brain. When brain development is complete, some purinergic mechanisms may be silenced, but may be reactivated in the adult brain/muscle, suggesting a role for purines in regeneration and self-repair. Thus, it is possible that guanosine-5′-triphosphate (GTP) also acts as regulator during the adult phase. However, regarding GBP, no specific receptor has been cloned for GTP or its metabolites, although specific binding sites with distinct GTP affinity characteristics have been found in both muscle and neural cell lines. Finally, even if the cross regulation mechanisms between the two different purines (ABP and GBP) are still largely unknown, it is now possible to hypothesize the existence of specific signal paths for guanosine-based nucleotides that are capable of modulating the intensity and duration of the intracellular signal, particularly in excitable tissues such as brain and muscle.

Raising the Guanosine-Based Molecules as Regulators of Excitable Tissues by the Exosomal-Vehiculated Signaling

“…Yet, Guo-based molecules must surely have an important role in signal transduction if excitable cells preserve plasma membrane-specific receptor binding sites, as demonstrated for the extracellular guanosine triphosphate (eGTP) both in murine myoblasts and rat neuron-like cells (Mancinelli et al, 2012;Mancinelli et al, 2020). In fact, eGTP stimulation has a role in myogenesis, via activation on myoblast plasma membranes, opening the intermediate calciumactivated potassium channels on the plasma membrane.…”

The wonder exerkines—novel insights: a critical state-of-the-art review

“…For example, a topic of interest is the purinergic signaling. Mancinelli and colleagues advocated for a major focus on guanosine-based purines acting on excitable tissues [ 60 ]. On this vein, Pietrangelo et al [ 61 ] recently pointed out the role of guanosine-based molecules in the muscle regeneration system.…”

Unfolding New Roles for Guanine-Based Purines and Their Metabolizing Enzymes in Cancer and Aging Disorders

“…For an in-depth description of the pathophysiological roles of GBPs in the central nervous system we direct readers to these reviews (Di Liberto et al, 2016;Tasca et al, 2018;Mancinelli et al, 2020).…”