Abstract：
:The gastrointestinal (GI) tract is exposed to a large array of proteases, under both physiological and pathophysiological conditions. The discovery of G protein-coupled receptors activated by proteases, the protease-activated receptors (PARs), has highlighted new signaling functions for proteases in the GI tract, particularly in the domains of inflammation and pain mechanisms. Activation of PARs by selective peptidic agonists in the intestine or the pancreas leads to inflammatory events and changes in visceral nociception, suggesting that PARs could be involved in the modulation of visceral pain and inflammation. PARs are present in most of the cells that are potentially actors in the generation of irritable bowel syndrome (IBS) symptoms. Activation of PARs interferes with several pathophysiological factors that are involved in the generation of IBS symptoms, such as altered motility patterns, inflammatory mediator release, altered epithelial functions (immune, permeability and secretory) and altered visceral nociceptive functions. Although definitive studies using genetically modified animals, and, when available, pharmacological tools, in different IBS and inflammatory models have not yet confirmed a role for PARs in those pathologies, PARs appear as promising targets for therapeutic intervention in visceral pain and inflammation processes.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Vergnolle Ndoi
10.1038/sj.bjp.0705750subject
Has Abstractpub_date
2004-04-01 00:00:00pages
1264-74issue
8eissn
0007-1188issn
1476-5381pii
sj.bjp.0705750journal_volume
141pub_type
杂志文章,评审abstract：:1. Inflammatory diseases of the pancreas or diseases which cause obstruction within the biliary or within the biliary or pancreatic duct system are associated with severe pain. Although neuropeptides such as substance P are present in the biliary tree, only few capsaicin-sensitive, substance P-positive nerve fibres ha...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1994.tb14772.x
更新日期：1994-02-01 00:00:00
abstract：:The prejunctional effects of clonidine and phenylephrine were studied in guinea-pig isolated atria by means of field stimulation of the sympathetic nerve terminals during the cardiac refractory period, in the presence of 1 microM atropine. Clonidine (10-100 nM) produced a dose-dependent decrease in the stimulus-inotro...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1984.tb10102.x
更新日期：1984-03-01 00:00:00
abstract：:1. The relationships between the density of dopamine D4.4 receptors and the agonist efficacies of L-745,870 (3-(4-[4-chlorophhenyl]piperazin-1-yl)-methyl-1H-pyrrolo [2, 3-b]pyridine) and U-101958 ((1-benzyl-piperidin-4-yl)-(3-isopropoxy-pyridin-2-yl)-methyl-a min e) were investigated in Chinese hamster ovary (CHO) cel...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0702849
更新日期：1999-10-01 00:00:00
abstract：:1. The effect of ondansetron, a selective 5-hydroxytryptamine3 (5-HT3) receptor antagonist, was studied in morphine-addicted rats. Morphine-dependence and tolerance, induced by drinking increasing concentrations of morphine sulphate in 5% sucrose solution for 3 weeks, were demonstrated by the naloxone-precipitated wit...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1996.tb15504.x
更新日期：1996-06-01 00:00:00
abstract：:1 The selectivity and specificity of RX 781094 [2-(2-(1,4 benzodioxanyl))2-imidazoline HCl] for alpha-adrenoceptors have been examined in peripheral tissues. 2 In isolated tissue experiments RX 781094 was a competitive antagonist at prejunctional alpha 2-adrenoceptors situated on the sympathetic nerve terminals of the...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1983.tb08809.x
更新日期：1983-03-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Memantine and ketamine are clinically used, open-channel blockers of NMDA receptors exhibiting remarkable pharmacodynamic similarities despite strikingly different clinical profiles. Although NMDA channel gating constitutes an important difference between memantine and ketamine, it is unclear how...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.13007
更新日期：2015-03-01 00:00:00
abstract：:There is evidence that cannabinoid-based medicines that are selective for different targets in the cannabinoid signalling system (e.g. receptors, inactivation mechanism, enzymes) might be beneficial in basal ganglia disorders, namely Parkinson's disease (PD) and Huntington's disease (HD). These benefits not only inclu...
journal_title：British journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1111/j.1476-5381.2008.00088.x
更新日期：2009-04-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Hepatic encephalopathy is a neuropsychiatric disorder of complex pathogenesis caused by acute or chronic liver failure. We investigated the effects of cannabidiol, a non-psychoactive constituent of Cannabis sativa with anti-inflammatory properties that activates the 5-hydroxytryptamine receptor 5...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.2010.01179.x
更新日期：2011-04-01 00:00:00
abstract：BACKGROUND AND PURPOSE:The homeostatic control of arterial BP is well understood with changes in BP resulting from changes in cardiac output (CO) and/or total peripheral resistance (TPR). A mechanism-based and quantitative analysis of drug effects on this interrelationship could provide a basis for the prediction of dr...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.12190
更新日期：2013-08-01 00:00:00
abstract：:1. The ability of memantine (1-amino-3,5-dimethyladamantane) to antagonize the modulatory effects of N-methyl-D-aspartate (NMDA) on phosphoinositide turnover stimulated by muscarinic cholinoceptor- and metabotropic glutamate receptor-agonists has been examined in neonatal rat cerebral cortex slices. 2. Memantine antag...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1995.tb13275.x
更新日期：1995-02-01 00:00:00
abstract：:Liver X receptors (LXRs) are members of the nuclear receptor superfamily that are canonically activated by oxidized derivatives of cholesterol. Since the mid-90s, numerous groups have identified LXRs as endocrine receptors that are involved in the regulation of various physiological functions. As a result, when their ...
journal_title：British journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1111/bph.15286
更新日期：2020-10-20 00:00:00
abstract：:1 Palmitaldehyde, olealdehyde and linolealdehyde acetal phosphatidic acids induced rapid shape change and dose-dependent biphasic aggregation of human platelets in platelet-rich plasma; aggregation was reversible at low doses and irreversible at high doses of the acetal phosphatidic acids. The palmitaldehyde congener ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1983.tb10508.x
更新日期：1983-05-01 00:00:00
abstract：:1. Histamine contracted the tracheal and major bronchial muscles of sheep and relaxed the muscles of the lesser bronchi and bronchioles.2. The stimulant action of histamine on the trachea was antagonized by mepyramine, whereas the relaxant effect on the bronchial tree was not.3. 5-Hydroxytryptamine contracted the musc...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1969.tb07997.x
更新日期：1969-07-01 00:00:00
abstract：:1. The subtype of alpha1-adrenoceptor mediating contractions to phenylephrine of the rat thoracic aorta, mesenteric artery and pulmonary artery were investigated by use of antagonists which show selectivity between the cloned alpha1-adrenoceptor subtypes in binding studies. 2. Cumulative concentration-contraction curv...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0701461
更新日期：1997-11-01 00:00:00
abstract：:A number of cholinoceptor antagonists used in the treatment of Parkinson's disease were examined for their ability to antagonize either the muscarinic receptor-mediated inhibition of dopamine D1 receptor-stimulated adenylyl cyclase or the muscarinic receptor-mediated stimulation of [3H]-inositol phosphates ([3H]-IPs) ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1996.tb15474.x
更新日期：1996-06-01 00:00:00
abstract：BACKGROUND AND PURPOSE:GABAA receptors mediate neuronal inhibition in the brain. They are the primary targets for benzodiazepines, which are widely used to treat neurological disorders including anxiety, epilepsy and insomnia. The mechanism by which benzodiazepines enhance GABAA receptor activity has been extensively s...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.13142
更新日期：2015-07-01 00:00:00
abstract：:1. The modulation of the gamma-aminobutyric acidA (GABAA) receptor by reduced metabolites of progesterone and deoxycorticosterone has been compared with that produced by depressant barbiturates in: (a) voltage-clamp recordings from bovine enzymatically isolated chromaffin cells in cell culture, and (b) an assay of the...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1988.tb11646.x
更新日期：1988-08-01 00:00:00
abstract：:1 The effect of local elevation of leucocyte cyclic adenosine 3',5'-monophosphate (cyclic AMP) content on the continued migration of leucocytes to a site of acute inflammation was studied in the pleural cavity of rats. 2 Leucocyte cyclic AMP levels were elevated by injecting with the irritant into the pleural cavity d...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1977.tb07742.x
更新日期：1977-06-01 00:00:00
abstract：:1. The effects of acetylcholine (ACh) on membrane potential, relaxation and cyclic GMP levels were compared to the NO donor L-nitrosocysteine (Cys-NO) in segments of guinea-pig coronary artery. 2. ACh and Cys-NO produced concentration-dependent relaxations of muscles contracted with the H1 receptor agonist, 2-(2-amino...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1994.tb14851.x
更新日期：1994-04-01 00:00:00
abstract：:1 A range of opioid receptor agonists were tested for activity in five antinociceptive models: the acetylcholine-induced abdominal constriction, tail-flick and hot plate tests in the mouse and the paw pressure test in the rat and guinea-pig. 2 Agonists acting preferentially at the kappa-opioid receptor were significan...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1987.tb11281.x
更新日期：1987-08-01 00:00:00
abstract：:1. The effects of capsaicin on voltage-gated Ca2+ currents (ICa), and intracellular Ca2+ concentrations [( Ca2+]i) in cultured dorsal root ganglion (DRG) neurones of the rat were examined in vitro by use of combined patch clamp-microfluorometric recordings. 2. Under voltage-clamp conditions, capsaicin (0.1-10 microM) ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1990.tb12725.x
更新日期：1990-10-01 00:00:00
abstract：:1. ZENECA ZD7288 (4-(N-ethyl-N-phenylamino)-1,2-dimethyl-6-(methylamino) pyrimidinium chloride, formerly ICI D7288) is a novel sino-atrial node function modulator which selectively slows sinus node rate. Its effects on haemodynamic function have been studied in pentobarbitone anaesthetized dogs, in comparison with zat...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1994.tb17101.x
更新日期：1994-11-01 00:00:00
abstract：:1. Perivascular nerves of the sheep middle cerebral artery show immunoreactivity for both vasoactive intestinal polypeptide (VIP) and calcitonin gene-related peptide (CGRP). 2. Rings of endothelium-denuded sheep middle cerebral artery precontracted with 5-hydroxytryptamine were relaxed by CGRP (maximum relaxation = 87...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1991.tb12213.x
更新日期：1991-03-01 00:00:00
abstract：:1. We investigated the role of adenosine 3':5'-cyclic monophosphate (cyclic AMP) in non-adrenergic non-cholinergic (NANC) contraction in guinea-pig bronchial strips. 2. Forskolin (3 nM to 1 microM) reduced NANC contraction induced by electrical field stimulation (EFS) in a concentration-dependent fashion (-log EC50 wa...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1992.tb09027.x
更新日期：1992-03-01 00:00:00
abstract：:1. The type of endothelin (ET) receptor located on the myenteric neurones of guinea-pig ileum was determined by receptor autoradiography and function of the receptor was examined by release experiments of acetylcholine (ACh) from the longitudinal muscle myenteric plexus (LM-MP) preparations. 2. Specific [125I]-ET-1 bi...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1996.tb15520.x
更新日期：1996-07-01 00:00:00
abstract：:In CHO cells transfected with the rat dopamine D2 receptor (long isoform), administration of dopamine per se elicited a concentration-dependent increase in arachidonic acid (AA) release. The maximal effect was 197% of controls (EC50=25 nM). The partial D2 receptor agonist, (-)-(3-hydroxyphenyl)-N-n-propylpiperidine [(...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0702025
更新日期：1998-08-01 00:00:00
abstract：:1. Nociceptive thresholds to noxious mechanical (paw pressure) and thermal (tail flick) stimuli were recorded in conscious rats. The effects of three selective kappa-opioid receptor agonists on the responses to these stimuli were determined following intravenous, intracerebroventricular or intrathecal administration. ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1988.tb10310.x
更新日期：1988-03-01 00:00:00
abstract：:HMG-CoA reductase inhibitors (statins) have now become one of the most powerful pharmacological strategies in the treatment of cardiovascular diseases. Originally, the cardioprotective effects of statins were thought to be mediated through lipid lowering actions. However, it has now become increasingly clear that the ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0706863
更新日期：2006-10-01 00:00:00
abstract：:1. The effects of intrathecally (i.t.) injected substance P (SP), neurokinin A (NKA), [beta-Ala8]NKA (4-10) and [MePhe7]neurokinin B (NKB) at T13 thoracic spinal cord level were investigated on renal excretion of water, sodium and potassium in the conscious saline-loaded rat. Antagonists selective for NK1 (RP 67580), ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0701223
更新日期：1997-07-01 00:00:00
abstract：:1. Tachycardia and bronchodilatation were produced by intravenous dimethylphenylpiperazinium iodide (DMPP) in the spinal or pithed cat. Responses other than those involving beta-adrenoceptors were minimized by appropriate blocking agents.2. With intact adrenals, both the tachycardia and bronchodilatation with 10 mug/k...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1973.tb08256.x
更新日期：1973-08-01 00:00:00
