page_title: Purinergic signalling
section_title: Nervous system
hierarchical_section_title: Purinergic signalling / Purinergic signalling in humans / Nervous system
caption_attribution_description: English: Purinergic signaling in microglia
context_page_description: Purinergic signalling is a form of extracellular signalling mediated by purine nucleotides and nucleosides such as adenosine and ATP. It involves the activation of purinergic receptors in the cell and/or in nearby cells, thereby regulating cellular functions.
  The purinergic signalling complex of a cell is sometimes referred to as the “purinome”.
context_section_description: In the central nervous system (CNS), ATP is released from synaptic terminals and binds to a plethora of ionotropic and metabotropic receptors. It has an excitatory effect on neurones, and acts as a mediator in neuronal–glial communications. Both adenosine and ATP induce astrocyte cell proliferation. In microglia, P2X and P2Y receptors are expressed. The P2Y6 receptor, which is primarily mediated by uridine diphosphate (UDP), plays a significant role in microglial phagoptosis, while the P2Y12 receptor functions as a specialized pattern recognition receptor. P2RX4 receptors are involved in the CNS mediation of neuropathic pain.
  In the peripheral nervous system, Schwann cells respond to nerve stimulation and modulate the release of neurotransmitters through mechanisms involving ATP and adenosine signalling. In the retina and the olfactory bulb, ATP is released by neurons to evoke transient calcium signals in several glial cells such as Muller glia and astrocytes. This influences various homeostatic processes of the nervous tissue including volume regulation and the control of blood flow. Although purinergic signaling has been connected to pathological processes in the context of neuron-glia communication, it has been revealed, that this is also very important under physiological conditions. Neurons possess specialised sites on their cell bodies, through which they release ATP (and other substances), reflecting their "well-being". Microglial processes specifically recognize these purinergic somatic-junctions, and monitor neuronal functions by sensing purine nucleotides via their P2Y12-receptors. In case of neuronal overactivation or injury, microglial processes respond with an increased coverage of neuronal cell bodies, and exert robust neuroprotective effects. Calcium signaling evoked by purinergic receptors contributes to the processing of sensory information.
  During neurogenesis and in early brain development, ectonucleotidases often downregulate purinergic signalling in order to prevent the uncontrolled growth of progenitor cells and to establish a suitable environment for neuronal differentiation.
caption: Microglial activation in the CNS via purinergic signalling
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