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 profound withdrawal syndrome precipitated by these antagonists in vivo. In this issue of the Journal, Divin et al. examined whether treatment of C6 glioma cells with mu-opioid receptor agonists produced constitutively active mu-opioid receptors or other commonly reported adaptations to prolonged agonist treatment. Adenylyl cyclase superactivation was readily apparent following agonist treatment but there was no evidence of the formation of constitutively active mu-opioid receptors. This result challenges the notion that prolonged agonist exposure inevitably produces mu* receptors, and is consistent with many studies of adaptations in neurons produced by chronic agonist treatment. The investigators provide no explanation of their failure to see mu* receptors in C6 cells, but this is perhaps understandable because the molecular nature of mu* receptors remains elusive, and the precise mechanisms that lead to their formation are unknown. Without knowing exactly what mu* receptors are, how they are formed and how they signal, understanding their role in cellular adaptations to prolonged opioid treatment will remain impossible. Studies such as this should refocus attention on establishing the molecular mechanisms that underlie that phenomenon of mu* receptors.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Connor Mdoi
10.1111/j.1476-5381.2009.00067.xsubject
Has Abstractpub_date
2009-04-01 00:00:00pages
1041-3issue
7eissn
0007-1188issn
1476-5381pii
BPH067journal_volume
156pub_type
评论,杂志文章abstract：:1. The contribution of nitric oxide (NO) and vasoactive intestinal polypeptide (VIP) to non-adrenergic non-cholinergic (NANC) relaxations in the pig gastric fundus was investigated. 2. Circular and longitudinal muscle strips were mounted for isotonic registration in the presence of atropine and guanethidine; tone was ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1995.tb16406.x
更新日期：1995-10-01 00:00:00
abstract：:1. Histamine and carbachol produced concentration-related increases in the accumulation of 3H-inositol phosphates in slices of bovine tracheal smooth muscle. 2. Noradrenaline alone produced a small stimulation of 3H-inositol phosphate accumulation which was inhibited by the alpha-adrenoceptor antagonist phentolamine. ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1988.tb11757.x
更新日期：1988-12-01 00:00:00
abstract：:1. Phenylarsine oxide (PAO) is commonly used to inhibit tyrosine phosphatase activity. However, PAO can affect a variety of different processes because of its ability to promote sulfhydryl oxidation. In the present study, we investigated the effects that PAO has on basal and beta-adrenergically stimulated L-type Ca(2+...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0705845
更新日期：2004-06-01 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：:The detrimental actions of leptin on cardiovascular function are well established. Smith et al. report the novel finding of a reduction of infarct size by exogenous leptin when given at reperfusion. The involvement of the reperfusion injury salvage kinase (RISK) pathway in such reduction of infarct size and its relati...
journal_title：British journal of pharmacology
pub_type： 评论,杂志文章
doi：10.1038/sj.bjp.0706833
更新日期：2006-09-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Excitation-transcriptional coupling involves communication between plasma membrane ion channels and gene expression in the nucleus. Calcium influx through L-type Ca(2+) channels induces phosphorylation of the transcription factor, cyclic-AMP response element binding protein (CREB) and downstream ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.2009.00599.x
更新日期：2010-03-01 00:00:00
abstract：:1. The regional binding of [3H]-(+)-5-methyl-10,11-dihydro-5H-dibenzo (a,d)cyclohepten-5,10-imine maleate ([3H]-(+)-MK 801) to sections of rat brain was measured by an in vitro quantitative autoradiographic technique. A heterogeneous distribution of binding sites was observed. 2. High values of binding were detected i...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1993.tb12845.x
更新日期：1993-03-01 00:00:00
abstract：:The effects of the opioid receptor agonist RX783006 and of the opioid receptor partial agonist (+)-meptazinol have been examined on electrically induced twitch responses of the guinea-pig isolated ileum and of the mouse isolated vas deferens. Log10 concentration-tissue state curves were determined for (+)-meptazinol a...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1986.tb10246.x
更新日期：1986-07-01 00:00:00
abstract：:1. Idioventricular rate responses and adrenoceptor number have been examined in normal Langendorff hearts perfused at 70 cmH2O and in 'ischaemic' hearts perfused at 10 cmH2O. 2. In hearts perfused at normal pressure, ventricular rate responses to phenylephrine in the presence of propranolol were biphasic with low conc...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1990.tb15860.x
更新日期：1990-07-01 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：:1. In the presence of atropine, mepyramine and ranitidine, electric field stimulation of the guinea-pig isolated ileum longitudinal muscle-myenteric plexus preparation resulted in a two component non-adrenergic non-cholinergic contraction. The initial contraction had a duration of approximately 1 s whereas the second ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1992.tb09036.x
更新日期：1992-03-01 00:00:00
abstract：:1. Exposure of depilated skin of guinea-pig to ultraviolet (u.v.) light for 20 s produces a prolonged inflammatory response.2. The erythaema becomes evident within 15-30 min after the exposure and progressively increases in intensity reaching its maximum by 4-6 hours. The erythaema persists over 24 hours.3. Increase i...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1973.tb08321.x
更新日期：1973-02-01 00:00:00
abstract：:Rodent models of chronic pain may elucidate pathophysiological mechanisms and identify potential drug targets, but whether they predict clinical efficacy of novel compounds is controversial. Several potential analgesics have failed in clinical trials, in spite of strong animal modelling support for efficacy, but there...
journal_title：British journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1111/j.1476-5381.2011.01300.x
更新日期：2011-10-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Sepsis is a systemic inflammatory response accompanied by excessive production of inflammatory cytokines and cardiovascular dysfunction. Importantly, macrophage-derived pro-inflammatory agents play a key role in cardiovascular impairment in sepsis. Here we have investigated the effects of trimeta...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.13386
更新日期：2016-02-01 00:00:00
abstract：:1 The binding of [3H]-5-hydroxytryptamine ([3H]-5-HT), [3H]-haloperidol and [3H]-dopamine to human blood platelets was investigated and the effects of unlabelled haloperidol on [3H]-5-HT binding and (+)- and (-)-butaclamol on [3H]-haloperidol were studied. 2 Scatchard analysis did not show any specific binding of [3H]...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1978.tb07812.x
更新日期：1978-07-01 00:00:00
abstract：:1. The effect of [Na]o on the catecholamine release evoked by K in ouabain pretreated, isolated adrenal glands of the cat, was investigated. 2. Reduction of [Na]o to 70, 50 and 25 mM, with sucrose as a substitute, did not modify the spontaneous catecholamine release but progressively increased the K (17.7 mM)-evoked s...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1989.tb12618.x
更新日期：1989-10-01 00:00:00
abstract：:Cyclic adenosine 3',5'-monophosphage (cyclic AMP) levels in guinea-pig tracheal rings increased on incubation with the vasoactive intestinal peptide (VIP). The effect was potentiated by the addition of theophylline. The results suggest that the tracheo-bronchial relaxant action of VIP may be mediated by stimulation of...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1978.tb08471.x
更新日期：1978-03-01 00:00:00
abstract：:1. Stimulation of the murine macrophage cell line RAW 264.7 with thapsigargin, an endomembrane Ca(2+)-ATPase inhibitor, induced histamine production in a time- and concentration-dependent manner. 2. The protein kinase C activator, 12-O-tetradecanoylphorbol 13-acetate (TPA), also enhanced histamine production. 3. alpha...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0703085
更新日期：2000-02-01 00:00:00
abstract：:The position of dose-response curves for histamine-induced accumulation of [3H]-inositol 1-phosphate ([3H]-IP1) in lithium-treated slices of guinea-pig brain prelabelled with [3H]-inositol differed significantly between cerebellum (EC50 5.1 +/- 1.0 microM) and cerebral cortex (EC50 16.3 +/- 0.7 microM). The Hill coeff...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1986.tb11186.x
更新日期：1986-12-01 00:00:00
abstract：:1. The effect of intravenous administration of dexamphetamine [+)-Amp) on rat pupil diameter was investigated. In all experiments, the vagosympathetic trunks were sectioned bilaterally at the cervical level. 2. In rats anaesthetized with urethane, (+)-Amp (0.1-0.3 mg kg-1, i.v.) produced a dose-related increase in pup...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1989.tb11781.x
更新日期：1989-01-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Evidence suggests that phosphorylation of TRPV1 is an important component underlying its aberrant activation in pathological pain states. To date, the detailed pharmacology of diverse TRPV1 receptor agonists and antagonists has yet to be reported for native TRPV1 under phosphorylating conditions....
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.12005
更新日期：2013-02-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Selective oestrogen receptor (ER) modulators (SERMs) are of great value in the treatment of breast cancer and osteoporosis. The aim of this study was to characterize pharmacologically a new class of SERMs synthesized based on the core structure of raloxifene. EXPERIMENTAL APPROACH:Competitive re...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0706960
更新日期：2007-01-01 00:00:00
abstract：:1. The effects of prolonged cold storage on the mechanical and membranal responses to stimulation of alpha- and beta-adrenoceptors by phenylephrine and isoprenaline, respectively, were studied on the guinea-pig taenia caecum.2. Cold storage invariably caused a decrease in the resting membrane potential, and this effec...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1972.tb08141.x
更新日期：1972-11-01 00:00:00
abstract：:1. The role of sodium-calcium exchanger in acetylcholine (Ach)-induced hyperpolarization of intact endothelial cells was studied in excised rat aorta. The membrane potential was recorded using perforated patch-clamp technique. 2. The mean resting potential of endothelial cells was -44.1+/-1.4 mV. A selective inhibitor...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0705866
更新日期：2004-09-01 00:00:00
abstract：:1. Human epicardial coronary artery rings, freshly obtained from cardiac transplant patients, were examined for their responses to endothelium-derived relaxing factor (EDRF)-releasing agents. 2. Functional antagonism profoundly influenced relaxation responses in this tissue. Increasing force with concentrations of U46...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1994.tb17109.x
更新日期：1994-12-01 00:00:00
abstract：:1. The effects of 3 competitive N-methyl-D-aspartate (NMDA) receptor antagonists, LY274614, LY233536 and LY235723, on the micturition reflex and external urethral sphincter EMG activity, were examined either under isovolumetric conditions or during continuous filling cystometry in urethane-anaesthetized (1.2 g kg-1, s...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1993.tb13774.x
更新日期：1993-09-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Pelitinib is a potent irreversible EGFR TK inhibitor currently in clinical trials for the treatment of lung cancer. Hyperthermia has been applied concomitantly with chemotherapy and radiotherapy to enhance treatment outcome. In this study, we investigated the ability of the combination of pelitin...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.13189
更新日期：2015-08-01 00:00:00
abstract：:The characteristics of the rat epidydimal adipocyte beta-adrenoceptor have been examined using lipolysis and cyclic AMP accumulation in adipocytes as well as adenylate cyclase activity in fat cell membranes. The pA2 values corrected for binding to bovine serum albumin of the selective antagonists betaxolol (beta 1-sel...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：
更新日期：1985-01-01 00:00:00
abstract：:Three neurotoxin homologues (CM10 and CM12 from Naja haje annulifera and S5C10 from Dendroaspis jamesoni kaimosae) and two short neurotoxins (CM14 from Naja haje annulifera and erabutoxin b from Laticauda semifasciata) were examined by circular dichroism (c.d.) and tested for neuromuscular activity on chick biventer c...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1984.tb10810.x
更新日期：1984-07-01 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
