1,721,305 research outputs found
Purinergic mechanosensory transduction and visceral pain
Full text linkIn 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
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 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
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
Multiple P2Y receptors couple to calcium-dependent, chloride channels in smooth muscle cells of the rat pulmonary artery
Full text linkUridine 5'-triphosphate (UTP) and uridine 5'-diphosphate (UDP) act via P2Y receptors to evoke contraction of rat pulmonary arteries, whilst adenosine 5'-triphosphate (ATP) acts via P2X and P2Y receptors. Pharmacological characterisation of these receptors in intact arteries is complicated by release and extracellular metabolism of nucleotides, so the aim of this study was to characterise the P2Y receptors under conditions that minimise these problems. ATP, UTP and UDP (10-4M) evoked oscillating, inward currents (peak = 13-727 pA) in 71-93% of cells. The first current was usually the largest and in the SPA the response to ATP was significantly greater than those to UTP or UDP (P < 0.05). Subsequent currents tended to decrease in amplitude, with a variable time-course, to a level that was significantly smaller for ATP (P < 0.05), UTP (P < 0.001) and UDP (P < 0.05) in the SPA. The frequency of oscillations was similar for each agonist (mean≈6-11.min-1) and changed little during agonist application. The non-selective P2 receptor antagonist suramin (10-4M) abolished currents evoked by ATP in SPA (n = 4) and LPA (n = 4), but pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS) (10-4M), also a non-selective P2 antagonist, had no effect (n = 4, 5 respectively). Currents elicited by UTP (n = 37) or UDP (n = 14) were unaffected by either antagonist. Contractions of SPA evoked by ATP were partially inhibited by PPADS (n = 4) and abolished by suramin (n = 5). Both antagonists abolished the contractions in LPA
P2X receptors: epithelial ion channels and regulators of salt and water transport.
Full text linkWhen the results from electrophysiological studies of renal epithelial cells are combined with data from in vivo tubule microperfusion experiments and immunohistochemical surveys of the nephron, the accumulated evidence suggests that ATP-gated ion channels, P2X receptors, play a specialized role in the regulation of ion and water movement across the renal tubule and are integral to electrolyte and fluid homeostasis. In this short review, we discuss the concept of P2X receptors as regulators of salt and water salvage pathways, as well as acknowledging their accepted role as ATP-gated ion channels
P2X purinoceptors in postmortem human cerebral arteries
No full textPharmacological studies have demonstrated that various purinoceptors are involved in the control of the cerebral vascular tone in many species. In this study, the existence of P2X purinoceptors in the postmortem human cerebral arteries was investigated with organ-bath pharmacology, autoradiography, and immunohistochemistry. Specimens were obtained from the M2 region of the middle cerebral arteries from human cadavers with an age range of 53-91 years and postmortem time of 37-54 h. Application of α,β- methylene adenosine triphosphate (ATP) produced concentration-dependent contraction in the arterial ring, whereas transmural nerve stimulation and noradrenaline did not elicit contraction. Autoradiography using [3H]α,β- methylene ATP (a radioligand for P2X purinoceptors) showed specific [3H]α,β-methylene ATP binding sites in the smooth-muscle cells of the postmortem human cerebral arteries. Immunohistochemistry with specific P2X1 purinoceptor antibodies revealed positive staining exclusively in the smooth muscle of the same specimens. All these results demonstrate the existence of P2X purinoceptors in human cerebral arteries, which were still functionally active despite the long postmortem time. The results from this study suggest that the postmortem human cerebral arteries can be useful specimens for studying the P2X purinoceptor-mediated responses
Characterisation of subtypes of the P2X and P2Y families of ATP receptors in the foetal human heart
No full textATP exerts a variety of actions within the myocardium, including the regulation of coronary vascular tone and modulation of the autonomic control of the heart. In order to characterise the ATP receptor subtypes involved in these effects, degenerate oligonucleotides were used to clone receptors of both P2X and P2Y families from the human foetal heart. About 1 ng of “Quick-Clone cDNA” from foetal human heart was subjected to amplification with two pairs of degenerate oligonucleotides designed to amplify subtypes of the P2X and P2Y receptor families by means of PCR reactions. The sequence analysis of 34 and 29 clones of the P2X and P2Y receptor families, respectively, demonstrated that P2X1, P2X3 and P2X4 subtypes are present in the human foetal heart together with P2Y6, P2Y2 and P2Y4 receptors. P2X1 and P2Y4 receptor subtypes were here characterised for the first time in the human foetal heart. The present study provides the first molecular characterisation of ATP receptors in the foetal human heart. The results show that many P2 receptor subtypes are expressed in the foetal human heart, perhaps contributing to developmental processes as well as to the activity of the foetal heart
Effects of calcium channel blockers on pharmacologically induced contractions of rainbow trout (Oncorhynchus mykiss) intestine
No full textPT: J; CR: BERRIDGE MJ, 1988, P R SOC LONDON B, V234, P359 BRINK C, 1981, J PHARMACOL EXP THER, V217, P592 BURKA JF, 1989, ANIMAL DRUGS FOOD SA, P110 BURKA JF, 1989, CAN J PHYSIOL PHARM, V67, P477 BURKA JF, 1990, IN PRESS CAN J PHYSL, V68 BURNSTOCK G, 1958, BRIT J PHARMACOL CHE, V13, P216 BURNSTOCK G, 1959, Q J MICROSC SCI, V100, P199 CARPENTER JR, 1986, J PHARMACOL METHOD, V15, P283 COOK DA, 1977, FED PROC, V36, P2584 HOAR WS, 1967, LABORATORY COMPANION ISHIKAWA S, 1985, BRIT J PHARMACOL, V86, P789 JANIS RA, 1983, BIOCHEM PHARMACOL, V32, P3499 JANIS RA, 1983, J MED CHEM, V26, P775 KARAKI H, 1988, LIFE SCI, V42, P111 KITCHEN I, 1984, TXB INVITRO PRACTICA LEFF P, 1987, J PHARMACOL EXP THER, V240, P284 SAIDA K, 1983, BLOOD VESSELS, V20, P105 SCHWARTZ A, 1984, ANNU REV MED, V35, P325 SMALL RC, 1982, BRIT J PHARMACOL, V77, P45 SPEDDING M, 1988, ANN NY ACAD SCI, V522, P248 VANBREEMEN C, 1979, PHARMACOL REV, V30, P167 WOLOWYK MW, 1987, J THERM BIOL, V12, P87; NR: 22; TC: 2; J9: FISH PHYSIOL BIOCHEM; PG: 7; GA: EG368Source type: Electronic(1
- …
