Abstract：
:1. Heterologous desensitization or intermolecular cross-talk plays a critical role in regulating intracellular signalling by diverse members of the G-protein-coupled receptor superfamily. We have previously established that the alpha and beta isoforms of the human thromboxane A(2) receptor (TP) undergo differential desensitization of signalling in response to 17 phenyl trinor prostaglandin (PG)E(2), an agonist of the EP(1) subtype of the PGE(2) receptor (EP) family. 2. Herein, we investigated the molecular basis of TPalpha and TPbeta desensitization in human embryonic kidney (HEK) 293 cells and in renal mesangial cells in response to 17 phenyl trinor PGE(2) and in response to the PGF(2alpha) receptor (FP) agonist PGF(2alpha), and sought to identify the target site(s) of those desensitizations. 3. Our results demonstrated that TPalpha and TPbeta receptors are subject to desensitization in response to both EP(1) and FP receptor activation and that these effects are mediated by direct protein kinase (PK)C phosphorylation of the individual TP isoforms within their unique carboxyl-terminal (C)-tail domains. 4. Moreover, deletion/site-directed mutagenesis and metabolic labelling studies identified Thr(337), within TPalpha, and Thr(399), within TPbeta, as the specific target residues for PKC phosphorylation and EP(1)- and FP-mediated desensitization of TPalpha and TPbeta signalling, respectively. 5. Hence, in conclusion, while the TPalpha and TPbeta diverge within their C-tail domains, they have evolved to share a similar mechanism of PKC-induced phosphorylation and desensitization in response to EP(1) and FP receptor activation, though it occurs at sites unique to the individual TP isoforms.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Kelley-Hickie LP,Kinsella BTdoi
10.1038/sj.bjp.0705695subject
Has Abstractpub_date
2004-05-01 00:00:00pages
203-21issue
1eissn
0007-1188issn
1476-5381pii
sj.bjp.0705695journal_volume
142pub_type
杂志文章abstract：:5-Hydroxytryptamine (5-HT, 5-160 microgram kg-1) injected intravenously in pentobarbitone-anaesthetized, open-chest cats caused dose-dependent increases in pulmonary arterial and intratracheal pressures. There was also a marked systemic hypotension and bradycardia. The pulmonary effects were completely prevented by ke...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1983.tb10033.x
更新日期：1983-10-01 00:00:00
abstract：:1. Recent studies demonstrated that inhibition or genetic inactivation of the enzyme poly (ADP-ribose) polymerase (PARP) is beneficial in myocardial reperfusion injury. PARP activation in the reperfused myocardium has been assumed, but not directly demonstrated. Furthermore, the issue whether pharmacological PARP inhi...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0704185
更新日期：2001-08-01 00:00:00
abstract：:1. TRPM2 is a Ca2+ -permeable nonselective cation channel activated by intracellular ADP-ribose (ADPR) and by hydrogen peroxide (H2O2). We investigated the modulation of TRPM2 activity by N-(p-amylcinnamoyl)anthranilic acid (ACA). ACA has previously been reported to inhibit phospholipase A2 (PLA2). 2. Using patch-clam...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0706739
更新日期：2006-06-01 00:00:00
abstract：:Mast cells participate in allergies, and also in immunity and inflammation by secreting proinflammatory cytokines. Flavonoids are naturally occurring polyphenolic plant compounds, one group of which -- the flavonols, inhibits histamine and some cytokine release from rodent basophils and mast cells. However, the effect...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0706246
更新日期：2005-08-01 00:00:00
abstract：:1 The effects of opioids on synaptic transmission in cat sacral parasympathetic colonic ganglia were studied in vitro, using intracellular electrophysiological techniques. Electrical stimulation of the pelvic nerve evoked fast excitatory postsynaptic potentials (e.p.s.ps), which were blocked by hexamethonium and tetro...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1987.tb11340.x
更新日期：1987-10-01 00:00:00
abstract：:1. We have previously found that human chymase cleaves big endothelins (ETs) at the Tyr31-Gly32 bond and produces 31-amino acid ETs (1-31), without any further degradation products. In this study, we investigated the effect of synthetic ET-1 (1-31) on the proliferation of cultured human coronary artery smooth muscle c...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0702141
更新日期：1998-11-01 00:00:00
abstract：:1. The effects of the muscarinic agonist carbachol on phosphoinositide metabolism and its relationship to alteration of intracellular calcium were examined in SK-N-SH human neuroblastoma cells. Muscarinic receptors on these cells are coupled to phospholipase C and the myo [2-3H]-inositol phosphates resulting from rece...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1989.tb12681.x
更新日期：1989-12-01 00:00:00
abstract：:Despite progression in anticancer drug development and improvements in the clinical utilization of therapies, current treatment regimes are still dependent upon the use of systemic antiproliferative cytotoxic agents. Although these agents are unquestionably potent, their efficacy is limited by toxicity towards 'normal...
journal_title：British journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1038/sj.bjp.0707657
更新日期：2008-04-01 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：:1. The mechanisms involved in tachykinin-induced oedema were investigated in rat skin and interactions between the tachykinins and calcitonin gene-related peptide (CGRP) were studied. 2. Intradermal injections of the tachykinins, substance P, neurokinin A and neurokinin B, stimulated local oedema formation which was i...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1989.tb11926.x
更新日期：1989-05-01 00:00:00
abstract：:1. We aimed to determine whether there are any changes in responsiveness of the mesenteric arterial beds to phenylephrine (Phe) and KCl in exercise-trained rats, and whether vascular endothelium and/or vascular smooth muscle play a role in these changes. 2. Adult male rats were subjected to a swimming schedule every d...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0702697
更新日期：1999-08-01 00:00:00
abstract：:1 4-Aminopyridine methiodide (4-APMI), a quaternary analogue of aminopyridine (4-AP), was tested for neuromuscular facilitatory actions on the chick biventer cervicis and frog sartorius nerve-muscle preparations. 2 In the chick, 4-APMI (10(-4) to 10(-2) M) augmented indirectly elicited twitches and reversed tubocurari...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1979.tb17333.x
更新日期：1979-01-01 00:00:00
abstract：:1. Protein phosphorylation is involved in the induction of nitric oxide synthase II (NOS II, iNOS) in several types of animal cells. Here we have investigated the possible involvement of major protein kinases in the induction of NOS II expression in human DLD-1 cells. 2. In DLD-1 cells, interferon--gamma alone induced...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0701782
更新日期：1998-04-01 00:00:00
abstract：:1 The action of iontophoretically administered lithium was studied on spinal Renshaw cells an interneurones and on supraspinal neurones in cerebral cortex, thalamus, hypothalamus and brain stem in anaesthetized cats and rats. 2 There was a correlation between the effects of Li+ and those of acetylcholine (ACh), althou...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1977.tb07740.x
更新日期：1977-06-01 00:00:00
abstract：:1. The effect of several clinically used dyes on prostaglandin E2 (PGE2) inactivation was studied in rat and human isolated lung. 2. All the dyes, given as infusions through the pulmonary circulation, inhibited the inactivation of PGE2 as measured by bioassay. The action of the dyes was readily reversible on stopping ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1981.tb09153.x
更新日期：1981-04-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Rho kinase (ROCK) activation is involved in neuroinflammatory processes leading to progression of neurodegenerative diseases such as Parkinson's disease. Furthermore, ROCK plays a major role in angiogenesis. Neuroinflammation and angiogenesis are mechanisms involved in developing l-DOPA-induced d...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.15275
更新日期：2020-12-01 00:00:00
abstract：:1. We have investigated the inhibitory effects of RP 73401 (piclamilast) and rolipram against human monocyte cyclic AMP-specific phosphodiesterase (PDE4) in relation to their effects on prostaglandin (PG)E2-induced cyclic AMP accumulation and lipopolysaccharide (LPS)-induced TNF alpha production and TNF alpha mRNA exp...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1996.tb15450.x
更新日期：1996-06-01 00:00:00
abstract：BACKGROUND AND PURPOSE:The aim of the present study was to assess the interaction of nitrergic neurotransmission within the bed nucleus of the stria terminalis (BNST) with local glutamatergic and noradrenergic neurotransmission in the control of cardiovascular responses to acute restraint stress in rats. EXPERIMENTAL ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.14447
更新日期：2018-10-01 00:00:00
abstract：BACKGROUND AND PURPOSE:The glucagon-like peptides GLP-1 and GLP-2 are secreted from enteroendocrine L-cells following nutrient ingestion. Drugs that increase activity of the GLP-1 axis are highly successful therapies for type 2 diabetes, and boosting L-cell secretion is a potential strategy for future diabetes treatmen...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.2011.01561.x
更新日期：2012-01-01 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. The effects of purinergic stimulation on action potential, force of contraction, 86Rb efflux and 45Ca uptake were investigated in guinea-pig left atria. 2. Adenosine exerted a negative inotropic effect which was antagonized by adenosine deaminase but enhanced by dipyridamole. 3. The negative inotropic effect of ade...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1989.tb12577.x
更新日期：1989-08-01 00:00:00
abstract：:1. We have investigated the effect of the potassium channel opener, NIP-121, on contraction elicited by melittin (a phospholipase A2 activator) in epithelium-intact and epithelium-denuded trachea isolated from guinea-pigs. The effects of NIP-121 were compared with those of isoprenaline, aminophylline and hydrocortison...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1993.tb13734.x
更新日期：1993-08-01 00:00:00
abstract：:In this issue, BJP is proud to publish an Endothelium Themed Section to celebrate the life of Robert F. Furchgott, who died on May 19th 2009. It is 30 years since he discovered endothelium-derived relaxant factor and a decade since he was awarded the Nobel Prize for this work. His discovery has led to an array of new ...
journal_title：British journal of pharmacology
pub_type： 社论
doi：10.1111/j.1476-5381.2009.00366.x
更新日期：2009-06-01 00:00:00
abstract：:The effect of a substance P antagonist, [D-Pro2, D-Trp7,9]-substance P (SPA), on gastric emptying and gastrointestinal transit in the rat was studied in order to elucidate a possible physiological role of endogenous substance P and other tachykinins in gastrointestinal motility. SPA was given by intraperitoneal inject...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1986.tb11144.x
更新日期：1986-11-01 00:00:00
abstract：:1. Various neurotransmitters in the brain regulate gastric acid secretion. Previously, we reported that the central injection of kappa-opioid receptor agonists stimulated this secretion in rats. Although the existence of kappa(1)-kappa(3)-opioid receptor subtypes has been proposed, the character is not defined. We inv...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0705082
更新日期：2003-03-01 00:00:00
abstract：:1 Pinacidil relaxes blood vessels through opening the K(ATP) channels with a resultant membrane hyperpolarization and inhibition of Ca(2+) influx. The aim of this study was to examine the mechanisms thereby pinacidil induces K(+) channel-independent relaxation in isolated endothelium-denuded rat mesenteric artery. 2 P...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0705062
更新日期：2003-02-01 00:00:00
abstract：:The effects of intravenous sufentanil and pre-administration of N-methyl-D-aspartate (NMDA) receptor antagonists were tested on a reflex triggered by C-fibre activation. The reflex was elicited by electrical stimulation of the sural nerve and recorded from the ipsilateral biceps femoris muscle in halothane anaesthetiz...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0704148
更新日期：2001-08-01 00:00:00
abstract：BACKGROUND AND PURPOSE:This paper is intended to assist pharmacologists to make the most of statistical analysis and in avoid common errors. APPROACH:A scenario is presented where an experimenter performed an experiment to test the effects of two drugs on cultured cells. Analysis of the results, expressed as percentag...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0707372
更新日期：2007-10-01 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：BACKGROUND AND PURPOSE:Endocannabinoids play an important role in modulating spinal nociceptive signalling, crucial for the development of pain. The cannabinoid CB1 receptor and the TRPV1 cation channel are both activated by the endocannabinoid anandamide, a product of biosynthesis from the endogenous lipid precursor N...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.13849
更新日期：2018-06-01 00:00:00
