Purinergic signalling during development and ageing

Abstract

Extracellular purines and pyrimidines play major roles during embryogenesis, organogenesis, postnatal development and ageing in vertebrates, including humans. Pluripotent stem cells can differentiate into three primary germ layers of the embryo but may also be involved in plasticity and repair of the adult brain. These cells express the molecular components necessary for purinergic signalling, and their developmental fates can be manipulated via this signalling pathway. Functional P1, P2Y and P2X receptor subtypes and ectonucleotidases are involved in the development of different organ systems, including heart, blood vessels, skeletal muscle, urinary bladder, central and peripheral neurons, retina, inner ear, gut, lung and vas deferens. The importance of purinergic signalling in the ageing process is suggested by changes in expression of A1 and A2 receptors in old rat brains and reduction of P2X receptor expression in ageing mouse brain. By contrast, in the periphery, increases in expression of P2X3 and P2X4 receptors are seen in bladder and pancreas.

Contribution of adenosine and ATP to the carotid body chemosensory activity in ageing

“…). In contrast with this up‐regulation of A 2A receptors, other authors have shown that adenosinergic activities were unaffected by ageing in the cerebellum and substantia nigra (for a review see Burnstock & Dale, ). Additionally, a reduction in P2X receptor expression in ageing mouse brain has been described as their role in glial synaptic current generation (Lalo et al .…”

“…For example, Canas et al (2009) demonstrated an up-regulation of A 2A receptors in ageing in the hippocampus, where those receptors are present presynaptically (Canas et al 2009) while in the CB A 2A receptors are present postsynaptically (Conde et al 2006a). In contrast with this up-regulation of A 2A receptors, other authors have shown that adenosinergic activities were unaffected by ageing in the cerebellum and substantia nigra (for a review see Burnstock & Dale, 2015). Additionally, a reduction in P2X receptor expression in ageing mouse brain has been described as their role in glial synaptic current generation (Lalo et al 2011).…”

Nociceptin/orphanin FQ up‐regulates P2X3 receptors in primary cultures of neonatal rat trigeminal ganglion neurons

“…Thus, the frequent co-expression of P2X 3 with ORL1 receptors in TG neurons, found in the present study, provides a possibility for P2X 3 receptor modulation by N/OFQ at single-cell level through activation of the ORL1 receptor. However, previous evidence showed that P2X 3 receptors had developmental roles and that the expression of P2X3 in TG neurons decreases with postnatal development (31,32); therefore, the distribution of P2X 3 -positive neurons, as well as the co-localization with ORL1, may be significantly different for adult trigeminal neurons, and any interactions seen in neonatal neurons may not replicate what occurs in adult neurons.…”

Why do premature newborn infants display elevated blood adenosine levels?

“…It was shown that most extracellular Ado derives from extracellular adenosine 5′-triphosphate (eATP), [18], due to the action of the widely distributed ectonucleotidases NTPDase I (CD39), and NT5E (CD73) on eATP. Signals delivered by eATP and Ado are transduced by functional P1, P2Y and P2X receptor subtypes, respectively [19]. ATP can be generated by oxidative phosphorylation occurring exclusively inside the mitochondrion, occasionally released outside the cells due to death or lysis.…”