Geoffrey Burnstock
University College Medical School, UK
Title: Purinergic Signalling in the Nervous System in Health and Disease
Biography
Biography: Geoffrey Burnstock
Abstract
The concept of purinergic neurotransmission (i.e. neurally released ATP acting as an extracellular signalling molecule) was proposed in 1972(Burnstock, 1972). Later it was recognised as a cotransmitter in most, if not all, nerves in the peripheral and central nervous systems, acting on post- and also pre-junctional membranes, at autonomic neuroeffector junctions and ganglionic and central synapses. ATP and its breakdown product adenosine also act as trophic factors during development and regeneration. Brief background information is given about ATP storage, release and ectoenzymatic breakdown. Purines and pyrimidines have key roles in neurotransmission and neuromodulation, with their effects being mediated by P1 (adenosine), P2X ion channel and P2Y G protein-coupled receptors. There is coverage of neuron-glia interactions and of purinergic neuroeffector transmission to non-muscular cells. Purinergic mechanisms and specific receptor subtypes have been shown to be involved in pathological conditions, including brain trauma and ischaemia, epilepsy, visceral and neuropathic pain, neurodegenerative diseases associated with neuroimmune and neuroinflammatory reactions, as well as neuropsychiatric diseases, including depression, anxiety and schizophrenia (see Burnstock, 2007). Specific purinergic receptor subtypes, notably A2A, P2X4 and P2X7 are being explored as therapeutic targets for the treatment of these conditions.