102,479 research outputs found
Purinergic signaling in the gastrointestinal tract
No full textGeoffrey Burnstock completed a BSc at King's College London and a PhD at University College London. He held postdoctoral fellowships with Wilhelm Feldberg (National Institute for Medical Research), Edith Bülbring (University of Oxford) and C. Ladd Prosser (University of Illinois). He was appointed to a Senior Lectureship in Melbourne University in 1959 and became Professor and Chairman of Zoology in 1964. In 1975 he became Head of Department of Anatomy and Developmental Biology at UCL and Convenor of the Center of Neuroscience. He has been Director of the Autonomic Neuroscience Institute at the Royal Free Hospital School of Medicine since 1997. He was elected to the Australian Academy of Sciences in 1971, the Royal Society in 1986, the Academy of Medical Sciences in 1998 and an Honorary Fellow of the Royal College of Surgeons and the Royal College of Physicians in 1999 and 2000. He was awarded the Royal Society Gold Medal in 2000. He is editor-in-chief of the journals Autonomic Neuroscience and Purinergic Signalling and on the editorial boards of many other journals. Geoffrey Burnstock's major research interest has been autonomic neurotransmission and he is best known for his seminal discovery of purinergic transmission and receptors, their signaling pathways and functional relevance. He has supervised over 100 PhD and MD students and published over 1400 original papers, re-views and books. He was first in the Institute of Scientific Information list of most cited scientists in Pharmacology and Toxicology from 1994-2004 [59.083 citations (March 2011) and an h-index of 109]
Purinergic mechanosensory transduction and visceral pain
No full textIn this review, evidence is presented to support the hypothesis that mechanosensory transduction occurs in tubes and sacs and can initiate visceral pain. Experimental evidence for this mechanism in urinary bladder, ureter, gut, lung, uterus, tooth-pulp and tongue is reviewed. Potential therapeutic strategies are considered for the treatment of visceral pain in such conditions as renal colic, interstitial cystitis and inflammatory bowel disease by agents that interfere with mechanosensory transduction in the organs considered, including P2X(3) and P2X(2/3) receptor antagonists that are orally bioavailable and stable in vivo and agents that inhibit or enhance ATP release and breakdown
Towards a revised nomenclature for P1 and P2 receptors
No full textThe classification of receptors for adenosine, ATP and ADP (collectively called purinoceptors) has seen a number of developments in the past three years. The important division of receptors into two major classes (1) adenosine (P1) receptors and (2) P2 purinoceptors, first suggested by Burnstock in 1978 (Ref.2), has been an abiding one that has set the stage for further subdivision of P2 purinoceptors into P2X and P2Y subtypes on the basis of pharmacological properties. Later, Dubyak summarized the evidence that ATP worked through two different transduction mechanisms: intrinsic ion channels and G protein-coupled receptors. This information, coupled with the cloning of purinoceptors in 1993/94, led Abbracchio and Burnstock to propose that purinoceptors should be classified in two families: G protein-coupled receptors termed P2Y purinoceptors, and intrinsic ion channels termed P2X purinoceptors. Developments in recent years have borne out these expectations and a revised nomenclature, essentially adopting the Abbracchio and Burnstock proposal, can now be proposed
Burnstock, Professor G.
No full textThis record was harvested from a previous catalogue system and will be withdrawn in 2025. Information in this record may be superseded or incomplete. Visit this record in UMA's new catalogue at: https://archives.library.unimelb.edu.au/nodes/view/435816Lasker Nomination, National Academy of Science US. Correspondence, articles, 2008.257785
Item: [2017.0015.00103] "Burnstock, Professor G.
Burnstock, Geoffrey: transcript of a video interview (10- and 11-Mar-2008)
No full textGeoffrey Burnstock has provided new insights about chemical neurotransmission in the autonomic nervous system where there are few specialised synapses, and transmitter release occurs from multiple points along a nerve fibre. For 30 years Burnstock pioneered an entirely new field of neuropharmacology known as “purinergic” based on his discovery that the purine derivatives adenosine and adenosine triphosphate (ATP) act as neurotransmitters or modulators in both the peripheral and central nervous system. This field has thrived in recent years with the discovery of multiple receptor subtypes. Currently major pharmaceutical industry efforts are developing new medicines for pain, cardiovascular disease and gastrointestinal diseases based on purinergic mechanisms. His work has had a major international impact, and in 2003 he was the most highly cited scientist in pharmacology and toxicology over the previous 10 years (Anonymous (2004) Geoffrey Burnstock: most highly cited scientist. Molecular Interventions 4: 192).Supported by a Wellcome Trust Public Engagement grant (2006-2008) in the History of Medicine to Professor Tilli Tansey (QMUL) and Professor Leslie Iversen (Oxford), this project recorded interviews with 12 prominent neuroscientists, between 2006 and 2008
PURINOCEPTORS - ARE THERE FAMILIES OF P2X AND P2Y PURINOCEPTORS
No full textThere has been an exponential growth in interest n purinoceptors since the potent effects of purines were first reported in 1929 and purinoceptors defined in 1978. A distinction between P1 (adenosine) and P2 (ATP/ADP) purinoceptors was recognized at that time and later, A1 and A2, as well as P2X and P2Y subclasses of P1 and P2 purinoceptors were also defined. However, in recent years, many new subclasses have been claimed, particularly for the receptors to nucleotides, including P2t, P2z, P2u(n) and P2D, and there is some confusion now about how to incorporate additional discoveries concerning the responses of different tissues to purines. The studies beginning to appear defining the molecular structure of P2-purinoceptors subtypes are clearly going to be important in resolving this problem, as well as the introduction of new compounds that can discriminate pharmacologically between subtypes. Thus, in this review, on the basis of this new data and after a detailed analysis of the literature, we propose that: 1. (1) P2X(ligand-gated) and P2Y(G-protein-coupled) puriceptor families are established: 2. (2) four subclasses of P2X-purinoceptor can be identified (P2X1-P2X4) to date; 3. (3) the variously named P2-purinoceptors that are G-protein-coupled should be incorporated into numbered subclasses of the P2Y family. Thus: 1. P2Y1 represents the recently cloned P2Y receptor (clone 803) from chick brain; 2. P2Y2 represents the recently cloned P2u (or P2n) receptor from neuroblastoma, human epithelial and rat heart cells; 3. P2Y3 represents the recently cloned P2Y receptor (clone 103) from chick brain that resembles the former P2t receptor; 4. P2Y4-P2Y6 represent subclasses based on agonist potencies of newly synthesised analogues; 5. P2Y7 represents the former P2D receptor for dinucleotides. This new framework for P2 purinoceptors would be fully consistent with what is emerging for the receptors to other major transmitters, such as acetylcholine, γ-aminobutyric acid, glutamate and serotonin, where two main receptor families have been recognised, one mediating fast receptor responses directly linked to an ion channel, the other mediating slower responses through G-proteins. We fully expect discussion on the numbering of the different receptor subtypes within the P2X and P2Y families, but believe that this new way of defining receptors for nucleotides, based on agonist potency order, transduction mechanisms and molecular structure, will give a more ordered and logical approach to accomodating new findings. Moreover, based on the extensive literature analysis that led to this proposal, we suggest that the development of selective antagonists for the different P2-purinoceptor subtypes is now highly desirable, particularly for therapeutic purposes
Purinergic signalling: past, present and future
No full textThe 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
Purinergic signalling: Pathophysiological roles
No full textIn this review, after a summary of the history and current status of the receptors involved in purinergic signalling, we focus on the distribution and physiological roles of purines and pyrimidines in both short-term events such as neurotransmission, exocrine and endocrine secretion and regulation of immune cell function, and long-term events such as cell growth, differentiation and proliferation in development and regeneration. Finally, the protective roles of nucleosides and nucleotides in events such as cancer, ischemia, wound healing, drug toxicity, inflammation and pain are explored and some suggestions made for future developments in this rapidly expanding field, with particular emphasis on the involvement of selective agonists and antagonists for purinergic receptor subtypes in therapeutic strategies
The involvement of purinergic signalling in obesity
No full textObesity is a growing worldwide health problem, with an alarming increasing prevalence in developed countries, caused by a dysregulation of energy balance. Currently, no wholly successful pharmacological treatments are available for obesity and related adverse consequences. In recent years, hints obtained from several experimental animal models support the notion that purinergic signalling, acting through ATP-gated ion channels (P2X), G protein-coupled receptors (P2Y) and adenosine receptors (P1), is involved in obesity, both at peripheral and central levels. This review has drawn together, for the first time, the evidence for a promising, much needed novel therapeutic purinergic signalling approach for the treatment of obesity with a âproof of conceptâ that hopefully could lead to further investigations and clinical trials for the management of obesity
Purinergic signalling and cancer
No full textReceptors for extracellular nucleotides are widely expressed by mammalian cells. They mediate a large array of responses ranging from growth stimulation to apoptosis, from chemotaxis to cell differentiation and from nociception to cytokine release, as well as neurotransmission. Pharma industry is involved in the development and clinical testing of drugs selectively targeting the different P1 nucleoside and P2 nucleotide receptor subtypes. As described in detail in the present review, P2 receptors are expressed by all tumours, in some cases to a very high level. Activation or inhibition of selected P2 receptor subtypes brings about cancer cell death or growth inhibition. The field has been largely neglected by current research in oncology, yet the evidence presented in this review, most of which is based on in vitro studies, although with a limited amount from in vivo experiments and human studies, warrants further efforts to explore the therapeutic potential of purinoceptor targeting in cancer
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