Abstract:
BACKGROUND AND PURPOSE:Thromboxane A(2) and endothelial dysfunction are implicated in the development of pulmonary hypertension. The receptor-transduction pathway for U46619 (9,11-dideoxy-9 alpha, 11 alpha-methanoepoxy prostaglandin F(2 alpha))-induced contraction was examined in endothelium-intact (E+) and denuded (E-) rat pulmonary artery rings. EXPERIMENTAL APPROACH:Artery rings were mounted on a wire myograph under a tension of 7-7.5 mN at 37 degrees C and gassed with 95% O(2)/5% CO(2). Isometric recording was made by using Powerlab data collection and Chart 5 software. KEY RESULTS:Both E+ and E- contractile responses were sensitive to Rho-kinase inhibition and the chloride channel blocker NPPB [5-nitro-2-(3-phenylpropylamino)benzoic acid]. The E+ response was sensitive to the store-operated calcium channel blockers SKF-96365 {1-[B-[3-(4-methoxyphenyl)propoxy]-4-methoxy-phenethyl]-1H-imidazole hydrochloride} and 2-APB (2-amino ethoxy diphenylborate) (75-100 micromol x L(-1)). The E- response was sensitive to 2-APB (10-30 micromol x L(-1)), a putative IP(3) receptor antagonist, and the calcium and chloride channel blockers nifedipine, DIDS (4,4'-diisothiocyanostilbene-2,2'-disulphonic acid) and niflumic acid but was insensitive to SKF-96365. Inhibiting K(V) with 4-AP in E+ rings exposed a contraction sensitive to nifedipine, DIDS and niflumic acid, whereas inhibiting BK(Ca) exposed a contraction sensitive to mibefradil, DIDS and niflumic acid. This indicates that removal of the endothelium allows the TP receptor to inhibit K(V), which may involve coupling to phospholipase C, because inhibition of phospholipase C with U73122 (1-[6-[[(17beta)-3-methoxyestra-1,3,5(10)-trien-17-y]amino]hexyl]- 1H-pyrrole-2,5-dione) switched the E- pathway to the E+ pathway. CONCLUSIONS AND IMPLICATIONS:The results from this study indicate that distinct transduction pathways can be employed by the TP receptor to produce contraction and that the endothelium is able to influence the coupling of the TP receptor.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
McKenzie C,MacDonald A,Shaw AMdoi
10.1111/j.1476-5381.2008.00084.xsubject
Has Abstractpub_date
2009-06-01 00:00:00pages
581-96issue
4eissn
0007-1188issn
1476-5381pii
BPH084journal_volume
157pub_type
杂志文章abstract::1 A rat isolated gastric mucosal preparation was used to monitor histamine output and acid secretion during stimulation by different secretagogues. 2 In non-stimulated preparations, spontaneous histamine output decreased over 450 min. 3 Stimulation of secretion with 4 (5)-methylhistamine or dibutyryl cyclic adenosine ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1982.tb09190.x
更新日期:1982-05-01 00:00:00
abstract:BACKGROUND AND PURPOSE:The effects of systemic treatment with indomethacin-loaded nanocapsules (IndOH-NC) were compared with those of free indomethacin (IndOH) in rat models of acute and chronic oedema. EXPERIMENTAL APPROACH:The following models of inflammation were employed: carrageenan-induced acute oedema (measured...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2009.00244.x
更新日期:2009-10-01 00:00:00
abstract::1 Non-adrenergic non-cholinergic (NANC) vasodilator nerves regulate tone in certain vascular beds. We have investigated the mechanisms of the NANC dilator response in the isolated small mesenteric artery of the rabbit by use of the tension myograph. 2 Small second or third order (150-300 microm in diameter) arteries o...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0701610
更新日期:1998-01-01 00:00:00
abstract:UNLABELLED:Midkine (MK) is a heparin-binding growth factor or cytokine and forms a small protein family, the other member of which is pleiotrophin. MK enhances survival, migration, cytokine expression, differentiation and other activities of target cells. MK is involved in various physiological processes, such as devel...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1111/bph.12353
更新日期:2014-02-01 00:00:00
abstract::1. The series of cycloalcohols C6, C7, C8 and C10 have been used to probe the molecular dimensions of a variety of general anaesthetic target sites. 2. The general anaesthetic EC50 concentrations of the cycloalcohols were determined for tadpoles (Xenopus laevis). All of the cycloalcohols tested were found to be potent...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1991.tb12148.x
更新日期:1991-01-01 00:00:00
abstract::1. The effects of brevetoxin-B, a red tide toxin, on motor nerve terminal activity were assessed on mouse triangularis sterni nerve-muscle preparations. The perineural waveforms were recorded with extracellular electrodes placed in the perineural sheaths of motor nerves. 2. At 0.11 microM, brevetoxin-B increased the c...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1991.tb12311.x
更新日期:1991-05-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Calu-3 cells are derived from serous cells of human lung submucosal glands, a prime target for therapy in cystic fibrosis (CF). Calu-3 cells can be cultured to form epithelia capable of transepithelial transport of chloride. A CF Calu-3 cell is not available. EXPERIMENTAL APPROACH:A retroviral v...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0707175
更新日期:2007-04-01 00:00:00
abstract::1. The psychoactive cannabinoids (-)-delta 9-tetrahydrocannabinol ((-)-delta 9-THC) and the 1,1-dimethyl-heptyl homologue of (-)-11-hydroxy-delta 8-tetrahydrocannabinol ((-)-DMH) both inhibited electrically-evoked contractions of the mouse isolated vas deferens and the myenteric plexus-longitudinal muscle preparation ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1992.tb09088.x
更新日期:1992-04-01 00:00:00
abstract::The histamine H3 receptor, first described in 1983 as a histamine autoreceptor and later shown to also function as a heteroreceptor that regulates the release of other neurotransmitters, has been the focus of research by numerous laboratories as it represents an attractive drug target for a number of indications inclu...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
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更新日期:2008-07-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Ca(2+)-dependent Cl(-) secretion (CaCC) in airways and other tissues is due to activation of the Cl(-) channel TMEM16A (anoctamin 1). Earlier studies suggested that Ca(2+) -activated Cl(-) channels are regulated by membrane lipid inositol phosphates, and that 1-O-octyl-2-O-butyryl-myo-inositol 3,...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2012.02193.x
更新日期:2013-01-01 00:00:00
abstract::1. The effects of long-term treatment with trandolapril, an angiotensin I-converting enzyme inhibitor, on exercise capacity of rats with chronic heart failure (CHF) following coronary artery ligation were examined. CHF was developed by 8 weeks after the coronary artery ligation. 2. The running time of rats with CHF in...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0702471
更新日期:1999-04-01 00:00:00
abstract::1. The vasodilator response to acetylcholine (ACh) was investigated in the aortic arches of the leopard frog (Rana pipiens). 2. With adrenaline pre-constricted preparations, both ACh and sodium nitroprusside (SNP) caused concentration-dependent relaxations. Damage to the endothelial layer abolished relaxations to ACh,...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1996.tb15568.x
更新日期:1996-07-01 00:00:00
abstract::1. Besides its antimuscarinic effects, propiverine may possess an additional mode of action. We compared the effects of propiverine, three of its metabolites (M-5, M-6, M-14) and atropine in human, pig and mouse urinary bladder preparations in order to elucidate the nature of a possible additional mode of action. 2. L...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0706244
更新日期:2005-07-01 00:00:00
abstract:BACKGROUND AND PURPOSE:N-docosahexaenoylethanolamine (DHEA) is the ethanolamine conjugate of the long-chain polyunsaturated n-3 fatty acid docosahexaenoic (DHA; 22: 6n-3). Its concentration in animal tissues and human plasma increases when diets rich in fish or krill oil are consumed. DHEA displays anti-inflammatory pr...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.12747
更新日期:2015-01-01 00:00:00
abstract::The effect of bath-applied luteinizing hormone-releasing factor (LHRF) was recorded in voltage-clamped bullfrog lumbar sympathetic neurones. At a holding potential of -- 30 mV, LHRF induced a steady inward (depolarizing) current and reduced membrane conductance; at -- 60 mV LHRF produced negligible inward current and ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1980.tb14547.x
更新日期:1980-03-01 00:00:00
abstract::1. Dopamine is assumed to affect the ovary function after its conversion into noradrenaline (NA). 2. To study this bovine luteal slices from 11-14 days of the oestrous cycle were preincubated for 24 h to recover beta-receptors and next they were incubated for 1, 2 or 4 h with (a) different doses of dopamine; (b) dopam...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1996.tb15590.x
更新日期:1996-08-01 00:00:00
abstract::1. The systemic and regional haemodynamic effects of the potassium channel activator EMD 52692 or its solvent were investigated after intravenous and after intracoronary administration in anaesthetized pigs. 2. Consecutive intravenous 10 min infusions of EMD 52692 (0.15, 0.30, 0.60, 1.20 micrograms kg-1 min-1; n = 7) ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1990.tb14128.x
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abstract::1. The role of alpha- and beta-adrenoceptor subtypes in the regulation of plasma glucose and immunoreactive insulin (IRI) levels has been investigated in normal conscious fasted rats by employing selective agonists and antagonists. 2. Adrenaline (0.2 mg kg-1)-induced hyperglycaemia was abolished by the selective alpha...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1990.tb14078.x
更新日期:1990-08-01 00:00:00
abstract::An approximate eight fold desensitization of the circular coat of the distal rabbit colon to adenosine 5'-triphosphate (ATP) and adenosine could be achieved by repeatedly exposing the organ to relatively low concentrations (10-100 microM) of these compounds. The desensitization was specific and reversible after prolon...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1982.tb08788.x
更新日期:1982-02-01 00:00:00
abstract::1. The ability of PD 128907 to activate dopamine receptors in the ventral tegmental area, substantia nigra pars compacta, and striatum was investigated by use of in vitro electrophysiological recording and fast cyclic voltammetry. The affinity of a novel D2 selective antagonist L-741,626 for receptors activated by thi...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1996.tb16063.x
更新日期:1996-12-01 00:00:00
abstract::Constitutively active mu-opioid receptors (mu* receptors) are reported to be formed following prolonged agonist treatment of cells or whole animals. mu* receptors signal in the absence of activating ligand and a blockade of mu* activation of G-proteins by naloxone and naltrexone has been suggested to underlie the prof...
journal_title:British journal of pharmacology
pub_type: 评论,杂志文章
doi:10.1111/j.1476-5381.2009.00067.x
更新日期:2009-04-01 00:00:00
abstract::1 Subcutaneous administration of glucagon (1 and 0.5 mg/kg) 30 min before the injection of carrageenin or dextran into the rat's paw reduced oedema and the local exudation of Evans blue previously given intravenously. 2 The effect persisted after removal of the adrenal medulla but not after adrenalectomy. 3 When gluca...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1975.tb07611.x
更新日期:1975-09-01 00:00:00
abstract::A study has been made of the pharmacology of the 5-hydroxytryptamine (5-HT)-induced depolarization responses that can be recorded extracellularly from the rat isolated cervical vagus nerve. Phenylbiguanide (PBG) and 2-methyl-5-hydroxytryptamine (2-methyl-5-HT) were found to mimic the effects of 5-HT on the vagus nerve...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1987.tb16844.x
更新日期:1987-01-01 00:00:00
abstract::1. We have characterized the human smooth muscle endothelin converting enzyme (ECE) present in the media of the endothelium-denuded human umbilical vein preparation. 2. Endothelin-1 (ET-1) and ET-2 were potent constrictors of umbilical vein with EC50 values of 9.2 nM and 29.6 nM, respectively. ET-1 was at least 30 tim...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0701564
更新日期:1997-12-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Cloxyquin (5-cloroquinolin-8-ol) has been described as an activator of TRESK (K2P 18.1, TWIK-related spinal cord K+ channel) background potassium channel. We have examined the specificity of the drug by testing several K2P channels. We have investigated the mechanism of cloxyquin-mediated TRESK a...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.13821
更新日期:2017-07-01 00:00:00
abstract:BACKGROUND:Macrophage elastase (MMP-12) is involved in the inflammatory process of chronic obstructive pulmonary disease (COPD). The aim of this study was to investigate in mice the effect of MMP-12 inhibition on the inflammatory process induced by cigarette smoke (CS) or by lipopolysaccharide (LPS) exposure of the air...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/bjp.2008.180
更新日期:2008-07-01 00:00:00
abstract::1 The effects of electrical stimulation, changes in external ion concentrations and various drugs on acetylcholine release from the myenteric plexus were measured by bioassay in the presence of physostigmine and by recording the responses of the longitudinal muscle. In preparations from the guinea-pig, the acetylcholi...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1978.tb17319.x
更新日期:1978-12-01 00:00:00
abstract::1 Contractions of the cat nictitating membrane were elicited on stimulation of the internal carotid nerve, and the effects were studied of desipramine and two inhibitors of catechol-O-methyltransferase, U-0521 and pyrogallol, on the subsequent relaxation of the muscle. 2 The relaxation of the nictitating membrane occu...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1978.tb07762.x
更新日期:1978-04-01 00:00:00
abstract::The effects of 10 mM caffeine (CAF) on intramembrane charge movements (ICM) were studied in isolated guinea-pig ventricular heart cells with the whole-cell patch-clamp technique. In the presence of CAF, the properties (voltage dependence, maximum Q(ON) [Q(max)], availability with voltage) of Q(ON) charge activated fro...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0704520
更新日期:2002-02-01 00:00:00
abstract::1. In the present study, we describe the expression of the neuropeptides vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) as well as their receptors in PC-3 cells, a human prostate cancer cell line. In addition, we have investigated their role in apoptosis induced by s...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0705317
更新日期:2003-07-01 00:00:00