TY - JOUR A1 - Burnstock, G JF - Brazilian Journal of Medical and Biological Research SN - 0100-879X UR - http://www.scielo.br/scielo.php?script=sci_serial&pid=0100-879X&lng=en&nrm=iso N1 - This work is published under a Creative Commons Attribution License (CC-BY). The authors retain ownership of the copyright for their article and can allow anyone to download, reuse, reprint, modify, distribute, and/or copy articles published in the BJMBR, as long as the original authors and source are cited. No permission is required from the authors or the publishers. IS - 1 SP - 3 VL - 42 KW - Purinoceptors P1 KW - P2X KW - P2Y KW - ATP release and breakdown KW - Purinergic neuropathology KW - Pain KW - Neurodegenerative diseases KW - CENTRAL-NERVOUS-SYSTEM KW - GATED ION CHANNELS KW - GUINEA-PIG KW - ATP RECEPTOR KW - ADENOSINE TRIPHOSPHATE KW - EXTRACELLULAR ATP KW - TAENIA-COLI KW - SYNAPTIC TRANSMISSION KW - MAMMALIAN NEURONS KW - STRUCTURAL MOTIF PB - ASSOC BRAS DIVULG CIENTIFICA ID - discovery1311081 N2 - The discovery of non-adrenergic, non-cholinergic neurotransmission in the gut and bladder in the early 1960's is described as well as the identification of adenosine 5'-triphosphate (ATP) as a transmitter in these nerves in the early 1970's. The concept of purinergic cotransmission was formulated in 1976 and it is now recognized that ATP is a cotransmitter in all nerves in the peripheral and central nervous systems. Two families of receptors to purines were recognized in 1978, P1 ( adenosine) receptors and P2 receptors sensitive to ATP and adenosine diphosphate ( ADP). Cloning of these receptors in the early 1990's was a turning point in the acceptance of the purinergic signalling hypothesis and there are currently 4 subtypes of P1 receptors, 7 subtypes of P2X ion channel receptors and 8 subtypes of G protein-coupled receptors. Both short-term purinergic signalling in neurotransmission, neuromodulation and neurosecretion and long-term ( trophic) purinergic signalling of cell proliferation, differentiation, motility, death in development and regeneration are recognized. There is now much known about the mechanisms underlying ATP release and extracellular breakdown by ecto-nucleotidases. The recent emphasis on purinergic neuropathology is discussed, including changes in purinergic cotransmission in development and ageing and in bladder diseases and hypertension. The involvement of neuron-glial cell interactions in various diseases of the central nervous system, including neuropathic pain, trauma and ischemia, neurodegenerative diseases, neuropsychiatric disorders and epilepsy are also considered. EP - 8 AV - public Y1 - 2009/01// TI - Purinergic signalling: past, present and future ER -