Abstract:
:Prostaglandin E(2) (PGE(2)) increased adenosine 3' : 5'-cyclic monophosphate (cyclic AMP) formation in tracheal epithelial cells and concomitantly decreased the production/secretion of immunoreactive endothelin (irET). Naturally occurring prostanoids and selective and non-selective EP receptor agonists showed the following rank order of potency in stimulating cyclic AMP generation by epithelial cells: PGE(2) (EP-selective)>16,16-dimethyl PGE(2) (EP-selective)>11-deoxy PGE(2) (EP-selective)>iloprost (IP/EP(1)/EP(3)-selective), butaprost (EP(2)-selective), PGD(2) (DP-selective), PGF(2alpha) (FP-selective). The lack of responsiveness of the latter prostanoids indicated that the prostanoid receptor present in these cells is not of the DP, FP, IP, EP(1), EP(2) or EP(3) subtype. Pre-incubating the cells with the selective TP/EP(4)-receptor antagonists AH23848B and AH22921X antagonized the PGE(2)-evoked cyclic AMP generation. This suggested that EP(4) receptors mediate PGE(2) effects. However, in addition to any antagonistic effects at EP(4)-receptors, both compounds, to a different extent, modified cyclic AMP metabolism. The selective EP(1), DP and EP(2) receptor antagonist (AH6809) failed to inhibit PGE(2)-evoked cyclic AMP generation which confirmed that the EP(2) receptor subtype did not contribute to the change in cyclic AMP formation in these cells. The PGE(2)-induced inhibition of irET production by guinea-pig tracheal epithelial cells was due to cyclic AMP generation and activation of the cyclic AMP-dependent protein kinase since this effect was reverted by the cyclic AMP antagonist Rp-cAMPS. These results provide the first evidence supporting the existence of a functional prostaglandin E(2) receptor that shares the pharmacological features of the EP(4)-receptor subtype in guinea-pig tracheal epithelial cells. These receptors modulate cyclic AMP formation as well as ET-1 production/secretion in these cells.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Pelletier S,Dubé J,Villeneuve A,Gobeil F Jr,Yang Q,Battistini B,Guillemette G,Sirois Pdoi
10.1038/sj.bjp.0703886subject
Has Abstractpub_date
2001-03-01 00:00:00pages
999-1008issue
5eissn
0007-1188issn
1476-5381journal_volume
132pub_type
杂志文章abstract:BACKGROUND AND PURPOSE:Intestinal mucositis is a common side-effect of irinotecan-based cancer chemotherapy regimens. This mucositis is associated with cytokine activation and NO synthesis. Production of IL-18 is up-regulated in patients suffering from inflammatory bowel disease. Therefore, we have investigated the rol...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.12584
更新日期:2014-05-01 00:00:00
abstract::1. Experiments were performed in anaesthetized rabbits to examine the effects of calcitonin gene-related peptide (CGRP) and the CGRP antagonist CGRP8-37 on blood flow to the medial collateral ligament of the knee joint. 2. Topical application of CGRP (10(-13) to 10(-9) mol) to the exposed external surface of eight kne...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0701265
更新日期:1997-08-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Toll-like receptor 4 (TLR4) signalling contributes to inflammatory cardiovascular diseases, but its role in hypertension and the associated vascular damage is not known. We investigated whether TLR4 activation contributed to angiotensin II (AngII)-induced hypertension and the associated vascular ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.13117
更新日期:2015-06-01 00:00:00
abstract::1. U937 cells are a continuous line of human cells of committed monocytic origin which serve as a useful model for studying human monocytic function. The present study investigated the effect of platelet-activating factor (Paf) on intracellular free calcium ion concentration ([Ca2+]i) in U937 cells using the calcium f...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1988.tb11461.x
更新日期:1988-04-01 00:00:00
abstract::1. In the present study the effect of N-methyl-D-aspartate (NMDA) on thromboxane B2 synthesis and on [Ca2+]i was studied in human platelets. 2. NMDA (10(-7) M) completely inhibited the synthesis of thromboxane B2 from exogenous arachidonic acid (AA), while it did not interfere with the aggregating effect of the thromb...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0701790
更新日期:1998-05-01 00:00:00
abstract:BACKGROUND AND PURPOSE:While arachidonyl ethanolamine (anandamide) produces pharmacological effects mediated by cannabinoid CB1 receptors, it is also an agonist at the transient receptor potential vanilloid type 1 (TRPV1) ion channel. This study examined the cellular actions of anandamide in the midbrain periaqueductal...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2010.01157.x
更新日期:2011-07-01 00:00:00
abstract::1. Series of analogues of acetylcholine have been prepared in which the acetyl group was replaced by phenylacetyl, cyclohexylacetyl, diphenylacetyl, dicyclohexylacetyl, (+/-)-phenylcyclohexylacetyl, benziloyl and (+/-)-phenylcyclohexylhydroxyacetyl groups and the trimethylammonium group was replaced by Me(2)EtN(+), Me...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1969.tb09539.x
更新日期:1969-09-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Pituitary adenylate cyclase-activating polypeptide (PACAP) is an excitatory neuropeptide with central and peripheral cardiovascular actions. Intrathecal PACAP increases splanchnic sympathetic nerve activity and heart rate, but not mean arterial pressure (MAP). We hypothesize that the three PACAP ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2012.02045.x
更新日期:2012-11-01 00:00:00
abstract:BACKGROUND AND PURPOSE:The Na+/Ca2+ exchanger (NCX) may contribute to triggered activity and transmural dispersion of repolarization, which are substrates of torsades de pointes (TdP) type arrhythmias. This study examined the effects of selective inhibition of the NCX by SEA0400 on the occurrence of dofetilide-induced ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2008.00096.x
更新日期:2009-03-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Δ9 -tetrahydrocannabinol (THC) acts via cannabinoid CB1 receptors to increase feeding. Here, we assessed the orexigenic effect of AM11101, a novel CB1 receptor agonist designed to have a more favourable pharmacodynamic profile than THC. EXPERIMENTAL APPROACH:The acute, orexigenic effects of AM11...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.14797
更新日期:2019-10-01 00:00:00
abstract::Inhibition of myocardial Ca2+ channels was investigated for three dihydropyridines with different structural features: Ro 18-3981, darodipine (PY 108-068) and nifedipine. Ro 18-3981 contains a sulphamoyl acetyl side-chain. In voltage-clamps experiments with isolated cardiac myocytes of guinea-pig, Ro 18-3981 caused a ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1987.tb08983.x
更新日期:1987-05-01 00:00:00
abstract::Using recently available selective agonists and antagonists we have examined further our postulate (Apperley et al., 1980) that 5-hydroxytryptamine (5-HT) mediates contraction of dog saphenous vein via a different 5-HT receptor type from that in the rabbit aorta. In the rabbit isolated aorta, ketanserin and spiperone ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1985.tb08948.x
更新日期:1985-11-01 00:00:00
abstract::1. The pulmonary vasculature is constantly exposed to oxygen and reactive oxygen species such as nitric oxide (NO) and superoxide anions which can combine at a near diffusion limited rate, to form the powerful, oxidant, peroxynitrite (ONOO-). When formed in large amounts, ONOO- is thought to contribute to tissue injur...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0701162
更新日期:1997-06-01 00:00:00
abstract::1. The role played by endogenous lipocortin 1 in the anti-migratory action exerted by dexamethasone (Dex) on monocyte recruitment in an in vivo model of acute inflammation was investigated by use of several neutralizing polyclonal antibodies raised against lipocortin 1 or a lipocortin 1-derived N-terminus peptide (pep...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0701029
更新日期:1997-03-01 00:00:00
abstract::Inotropic actions of the endogenous enkephalins, leucine enkephalin [( Leu] enkephalin) and methionine enkephalin [( Met] enkephalin), and derivatives, [D-Ala2-methionine] enkephalinamide (DAMEA) and [D Ala2-leucine]enkephalinamide (DALEA) were tested, alone or in combination with noradrenaline (NA), (+/-)-isoprenalin...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1985.tb08888.x
更新日期:1985-06-01 00:00:00
abstract::The vasorelaxant activity of eicosapentaenoic acid (EPA, 20:5n-3), the omega-3 polyunsaturated fatty acid, was investigated in isolated Wistar Kyoto (WKY) rat aortae by measuring isometric tension. Eicosapentaenoic acid (1 - 100 microM) relaxed rat aortae contracted with high K(+) (80 mM) or noradrenaline (NA, 1 micro...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0703754
更新日期:2000-12-01 00:00:00
abstract::1 We have examined the effect of the histone deacetylase inhibitors apicidin, trichostatin A (TSA) and n-butyrate on the histone acetylation and the differentiation of human eosinophilic leukemia HL-60 clone 15 cells into eosinophils. 2 Viability of the cells incubated with apicidin (100 nm), TSA (30 nm) or n-butyrate...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0705869
更新日期:2004-07-01 00:00:00
abstract::Glucagon-like peptide 1 (GLP-1) is a relatively recently discovered molecule originating in the so-called L-cells of the intestine. The peptide has insulinotrophic properties and it is this characteristic that has predominantly been investigated. This has led to the use of the GLP-1-like peptide exendin-4 (EX-4), whic...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1111/j.1476-5381.2009.00486.x
更新日期:2010-02-01 00:00:00
abstract::The effect of propranolol, a beta-adrenoceptor blocking agent, has been investigated on gastric acid secretion in pylorus and cardiac-ligated rats. Compared to the control group, propranolol significantly diminished the gastric acid secretion, and inhibited the formation of gastric ulceration. ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1972.tb06860.x
更新日期:1972-09-01 00:00:00
abstract::1 The prostaglandin synthesizing enzymes were found to be present in fat cell ghosts isolated from rabbit adipose tissue. 2 Prostaglandin E2 (PGE2) and PGF2, were synthesized by ghosts after stimulation with adrenocorticotrophic hormone (ACTH). 3 Indomethacin was found to inhibit this synthesis but not the synthesis o...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:
更新日期:1979-11-01 00:00:00
abstract::1. Juvenile male rats treated with parachlorophenylalanine showed hair loss round the head and neck extending down the chest and abdomen.2. Treated isolated rats did not have this loss of hair, while untreated animals living in the same cage as treated rats lost their hair. The loss therefore seems to be caused by inc...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1970.tb08518.x
更新日期:1970-02-01 00:00:00
abstract::1 Noradrenaline and clonidine were applied by microiontophoresis to single neurones in the cerebral cortex and medullary reticular formation of anaesthetized rats.2 Of a total of 247 neurones studied, 79% of medullary units and 60% of cortical units responded in the same manner to both noradrenaline and clonidine. The...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1974.tb10670.x
更新日期:1974-07-01 00:00:00
abstract::1. To characterize the muscarinic receptors on human pulmonary veins associated with the acetylcholine (ACh)-induced relaxation, isolated venous and arterial preparations were pre-contracted with noradrenaline (10 microM) and were subsequently challenged with ACh in the absence or presence of selective muscarinic anta...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0703301
更新日期:2000-05-01 00:00:00
abstract::Authentic nitric oxide (NO; 0.1 - 10 micromoles) caused transient, dose-dependent relaxation of phenylephrine-induced tone without changing membrane potential in mesenteric arteries. Larger doses, above 10 micromoles, did not evoke more relaxation (maximal relaxation to 150 micromoles NO in denuded arteries, 69+/-7%, ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0704127
更新日期:2001-07-01 00:00:00
abstract::1. We examined the effect of the sulphonylurea glimepiride on three types of recombinant ATP-sensitive potassium (K(ATP)) channels. 2. K(ATP) channels share a common pore-forming subunit, Kir6.2, which associates with different sulphonylurea receptor isoforms (SUR1 in beta-cells, SUR2A in heart and SUR2B in smooth mus...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0704062
更新日期:2001-05-01 00:00:00
abstract::1 The effects of alpha- and beta-adrenoceptor stimulants on the histamine-forming capacity (HFC) of human isolated leucocytes have been studied, in vitro.2 It was confirmed that antigen significantly stimulates the HFC of human leucocytes.3 beta-Adrenoceptor stimulants, such as isoprenaline and salbutamol (10(-6)-10(-...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1974.tb09702.x
更新日期:1974-10-01 00:00:00
abstract::The presence of functional cannabinoid CB2 receptors in the CNS has provoked considerable controversy over the past few years. Formerly considered as an exclusively peripheral receptor, it is now accepted that it is also present in limited amounts and distinct locations in the brain of several animal species, includin...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1038/sj.bjp.0707505
更新日期:2008-01-01 00:00:00
abstract::1. Effects of morphine sulphate (1.25, 2.5, 5, 10, 20 and 40 mg/kg i.p.) on locomotor activity of male rats were observed for 8 h after single doses in non-tolerant rats. The lower three doses had only an excitatory effect, whereas the higher three doses caused initial depression followed by a delayed excitatory effec...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1972.tb06866.x
更新日期:1972-10-01 00:00:00
abstract::1. To clarify the role of the first thrombin receptor/protease-activated receptor (PAR)-1 in an inflammatory process, we tested and characterized the effect of intraplantar (i.pl.) administration of the highly specific PAR-1 agonist TFLLR-NH2 in rat hindpaw. 2. TFLLR-NH2 administered i.pl. at 0.01-0.03 micromol per pa...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0702513
更新日期:1999-04-01 00:00:00
abstract::1 gamma-Aminobutyric acid (GABA, 0.1 to 1 mM) had no significant effect on the amplitude, rise time, half decay time or frequency of miniature endplate potentials (m.e.p.ps) at the frog or mouse neuromuscular junctions in vitro. 2 Addition of GABA (1 mM) to preparations previously treated with 11 mM K+-Ringer did not ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1980.tb10937.x
更新日期:1980-01-01 00:00:00