Abstract:
:1 Endomorphin-1 and -2 (E-1/E-2) have been proposed as endogenous ligands for the mu-opioid receptor. The aims of this study are to characterize the binding of E-1/E-2 and the subsequent effects on cyclic AMP formation and [Ca2+]i levels in SH-SY5Y and Chinese hamster ovary (CHO) cells expressing endogenous and recombinant mu-opioid receptors. 2 E-1 displaced [3H]-diprenorphine ([3H]-DPN) binding in CHO micro and SH-SY5Y membranes with pKi values of 8.02+/-0.09 and 8.54+/-0.13 respectively. E-2 displaced [3H]-DPN binding in CHOmu and SH-SY5Y cells with pKi values of 7.82+/-0.11 and 8.43+/-0.13 respectively. E-1/E-2 bound weakly to CHOdelta and CHOkappa membranes, with IC50 values of greater than 10 microM. 3 In CHOmu cells, E-1/E-2 inhibited forskolin (1 microM) stimulated cyclic AMP formation with pIC50 values of 8.03+/-0.16 (Imax = 53.0+/-9. 3%) and 8.15+/-0.24 (Imax = 56.3+/-3.8%) respectively. In SH-SY5Y cells E1/E2 inhibited forskolin stimulated cyclic AMP formation with pIC50 values of 7.72+/-0.13 (Imax=46.9+/-5.6%) and 8.11+/-0.31 (Imax = 40.2+/-2.8%) respectively. 4 E-1/E-2 (1 microM) increased [Ca2+]i in fura-2 loaded CHOmu cell suspensions in a thapsigargin sensitive and naloxone reversible manner. Mean increases observed were 106+/-28 and 69+/-6.7 nM respectively. In single adherent cells E-1/E-2 (1 microM) increased [Ca2+]i with a mean 340/380 ratio change of 0.81+/-0.09 and 0.40+/-0.08 ratio units respectively. E-1/E-2 failed to increase intracellular calcium in CHOdelta, CHOkappa and SH-SY5Y cells. 5 These data show that E-1/E-2 bind with high affinity and selectivity to mu-opioid receptors and modulate signal transduction pathways typical of opioids. This provides further evidence that these two peptides may be endogenous ligands at the mu-opioid receptor.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Harrison C,McNulty S,Smart D,Rowbotham DJ,Grandy DK,Devi LA,Lambert DGdoi
10.1038/sj.bjp.0702798subject
Has Abstractpub_date
1999-09-01 00:00:00pages
472-8issue
2eissn
0007-1188issn
1476-5381journal_volume
128pub_type
杂志文章abstract:BACKGROUND AND PURPOSE:Up-regulation of thioredoxin interacting protein (TXNIP), an endogenous inhibitor of thioredoxin (Trx), compromises cellular antioxidant and anti-apoptotic defences and stimulates pro-inflammatory cytokines expression, implying a role for TXNIP in apoptosis. Here we have examined the causal role ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2011.01336.x
更新日期:2011-09-01 00:00:00
abstract::1 The metabolism of prostacyclin (PGI2) and 6-keto prostaglandin F1 alpha (6-keto PGF1 alpha) was studied in cell-free homogenates of rat, rabbit and guinea-pig kidney. 2 Rabbit kidney converted both PGI2 and 6-keto PGF1 alpha to a stable metabolite with chromatographic and biological activity identical to that of aut...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1983.tb10507.x
更新日期:1983-05-01 00:00:00
abstract::1. The purpose of this investigation was to examine the outputs of peptide histidine isoleucine (PHI) and vasoactive intestinal peptide (VIP) from the gastric corpus in response to stimulation of the peripheral (PVS) and central (CVS) ends of the vagus nerve and to compare the effects of PHI on gastric motility and bl...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1990.tb15787.x
更新日期:1990-06-01 00:00:00
abstract::1 The relative potencies of methotrimeprazine, (+)-methotrimeprazine, (+/-)-10-(3-dimethylamino-2-methylpropyl)-2-valeroyl phenothiazine hydrochloride (M & B 18,706) and (+)-M & B 18,706 in reducing the pressor action of noradrenaline in the spinal cat, reducing intercollicular decerebrate rigidity, and muscle spindle...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1974.tb09610.x
更新日期:1974-03-01 00:00:00
abstract::1. We have investigated the effect of phorbol esters and the down-regulation of protein kinase C on contraction of guinea-pig ileum longitudinal smooth muscle to carbachol and high K+. 2. Phorbol 12,13-dibutyrate (PDBu) enhanced the phasic component and inhibited or enhanced, respectively, the tonic component of contr...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1989.tb14607.x
更新日期:1989-11-01 00:00:00
abstract:BACKGROUND AND PURPOSE:mTOR inhibitors are currently used as immunosuppressants in transplanted patients and as promising anti-cancer agents. However, new-onset diabetes is a frequent complication occurring in patients treated with mTOR inhibitors such as rapamycin (Sirolimus). Here, we investigated the mechanisms asso...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2011.01716.x
更新日期:2012-04-01 00:00:00
abstract::1. Isolated tissues of the guinea-pig were bathed with Krebs solution at 37 degrees C and subjected to 100 ms pulses of electrical stimulation for 30 min at a frequency of 0.1 or 1.0 Hz. The tissues were then dried, ashed, and the ash analysed for calcium, sodium, potassium and magnesium.2. Gastric smooth muscle, card...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1972.tb08124.x
更新日期:1972-08-01 00:00:00
abstract::1. The effects of suramin on an adenosine 5'-triphosphate (ATP)-activated inward current were investigated in PC12 phaeochromocytoma cells with whole-cell voltage-clamp techniques. 2. Suramin (30 to 300 microM) inhibited the ATP-activated current in a dose-dependent manner. The inhibitory effects were reversible and c...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1990.tb12117.x
更新日期:1990-09-01 00:00:00
abstract::1. Neurally-evoked output of newly synthesized [3H]-acetylcholine from the rat phrenic nerve was measured in the absence of cholinesterase inhibitors. 2. Noradrenaline and isoprenaline enhanced neurally-evoked transmitter output markedly. Moreover, immediately after the application of noradrenaline the basal tritium e...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1988.tb11574.x
更新日期:1988-07-01 00:00:00
abstract::1. Lowering of the extracellular Mg(2+)-concentration induces various patterns of epileptiform activity in combined rat entorhinal cortex-hippocampal brain slices. After a prolonged period of exposure to Mg(2+)-free medium seizure-like events in the entorhinal cortex change to a state of late recurrent discharges whic...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1996.tb15710.x
更新日期:1996-10-01 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::The non-peptide NK1 receptor antagonist, CP-96,345, and its 2R,3R enantiomer CP-96,344, which is not an NK1 receptor antagonist (IC50 > 10 microM), were evaluated for antinociceptive and anti-inflammatory activities in several classical models of pain and inflammation in the rat. Both CP-96,345 and CP-96,344 reduced c...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1992.tb12737.x
更新日期:1992-10-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Benzofurans are newly used psychoactive substances, but their pharmacology is unknown. The aim of the present study was to pharmacologically characterize benzofurans in vitro. EXPERIMENTAL APPROACH:We assessed the effects of the benzofurans 5-APB, 5-APDB, 6-APB, 6-APDB, 4-APB, 7-APB, 5-EAPB and ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.13128
更新日期:2015-07-01 00:00:00
abstract::1. In circular smooth muscle of the guinea-pig gastric fundus, transmural nerve stimulation evoked a cholinergic excitatory junction potential (e.j.p.), and blockade of the e.j.p. by atropine revealed a non-adrenergic non-cholinergic (NANC) inhibitory junction potential (i.j.p.). 2. The amplitude of the e.j.p. was inc...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1996.tb15290.x
更新日期:1996-03-01 00:00:00
abstract::1. A series of 5-hydroxytryptamine (5-HT) receptor agonists including 5-HT, 5-carboxamidotryptamine (5-CT) and sumatriptan produced little or no contraction of rabbit isolated mesenteric arteries under resting tone conditions, even at concentrations up to 10(-4) M. 2. When the same agonists were retested in mesenteric...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1995.tb13228.x
更新日期:1995-01-01 00:00:00
abstract::The physiological regulation of the immune system encompasses comprehensive anti-inflammatory mechanisms that can be harnessed for the treatment of infectious and inflammatory disorders. Recent studies indicate that the vagal nerve, involved in control of heart rate, hormone secretion and gastrointestinal motility, is...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1038/sj.bjp.0707264
更新日期:2007-08-01 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:BACKGROUND AND PURPOSE:Bortezomib (Velcade®) is a breakthrough treatment for multiple myeloma, significantly improving patient survival. However, its use is limited by painful neuropathy often resulting in dose reduction/cessation of first-line treatment due to lack of treatment. The aim of this study was to characteri...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.14063
更新日期:2017-12-01 00:00:00
abstract::1. The role of alpha2-adrenoceptor (AR) subtypes in the modulation of acute nociception, motor behaviour and body temperature, has been investigated by determining the activity of the alpha2AR selective agonist dexmedetomidine (Dex) in mice devoid of individual alpha2AR subtypes through either a point (alpha2A) or nul...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0701520
更新日期:1997-12-01 00:00:00
abstract::1. The atrioventricular node (AVN) is an important part of the conduction system in the heart and is a significant site of antiarrhythmic drug action. The class 1 antiarrhythmic propafenone is effective in treating a variety of arrhythmias, including those involving the AVN. In this study, we have investigated the eff...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0701086
更新日期:1997-05-01 00:00:00
abstract::1. The effect of the potassium channel openers, NIP-121 and cromakalim, on agonist-induced relaxation of the guinea-pig isolated trachea was investigated and the results were compared with those in the epithelium-denuded trachea. 2. Tracheal strips were incubated with a potassium channel opener or vehicle for 30 min i...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1992.tb13416.x
更新日期:1992-12-01 00:00:00
abstract::I.c.v. self-administration of MDMA (0.01-2 micro g per infusion), alone and in combination with CP 55,940 (0.4 micro g infusion(-1)), was studied on an operant responding procedure. On the basis of individual preference for one of two levers, developed during training, rats were allowed to self-administer vehicle from...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0704825
更新日期:2002-08-01 00:00:00
abstract::5-Lipoxygenase (5-LO) is a crucial enzyme in the synthesis of the bioactive leukotrienes (LTs) from arachidonic acid (AA), and inhibitors of 5-LO are thought to prevent the untowarded pathophysiological effects of LTs. In this study, we present the molecular pharmacological profile of the novel nonredox-type 5-LO inhi...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0705860
更新日期:2004-07-01 00:00:00
abstract::1. An investigation was carried out to determine if the sympathoinhibition caused by urapidil is due to activation of 5-HT1A receptors by investigating whether it could be reversed by the non-selective 5-HT1A receptor antagonist spiperone. To control for the possibility of functional antagonism by spiperone, the abili...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1991.tb12290.x
更新日期:1991-04-01 00:00:00
abstract::1. The distribution and some pharmacological properties of centrally located dextromethorphan high-affinity binding sites were investigated by in vitro autoradiography. 2. Sodium chloride (50 mM) induced a 7 to 12 fold increase in dextromethorphan binding to rat brain in all areas tested. The effect of sodium was conc...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0701043
更新日期:1997-04-01 00:00:00
abstract::1 The response of pentobarbitone-anaesthetized cats to the intravenous administration of E. coli endotoxin (2 mg/kg) consisted of acute pulmonary vasoconstriction (3-5 min after the injection) and a secondary shock phase characterized by delayed systemic hypotension, decreased central venous pressure and cardiac outpu...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1974.tb08559.x
更新日期:1974-02-01 00:00:00
abstract::1. Opioid agonists inhibit neurogenic mucus secretion in the airways. The mechanism of the inhibition is unknown but may be via opening of potassium (K+) channels. We studied the effect on neurogenic secretion in ferret trachea in vitro of the OP1 receptor (formerly known as delta opioid receptor) agonist [D-Pen2,5]en...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0701786
更新日期:1998-04-01 00:00:00
abstract::To evaluate the role of G-protein-coupled receptor kinases (GRK) in the desensitization of the histamine H(2) receptor, the H(2) receptor was transiently cotransfected with GRK2, 3, 5 or 6 in COS-7 cells and the cyclic AMP levels in response to histamine were studied. Coexpression of the H(2) receptor with GRK2 and 3 ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0703676
更新日期:2000-12-01 00:00:00
abstract::1. Insulin antibodies were induced in young guinea-pigs of both sexes weighing 300-400 g and housed in a room maintained at 28 degrees C+/-2 degrees C, by subcutaneous injection of 2 ml of freshly prepared insulin antigen emulsion between the shoulders once every month.2. To estimate the titre of serum antibody the se...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1971.tb07087.x
更新日期:1971-05-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Peptide YY (PYY) and neuropeptide Y (NPY) activate Y receptors, targets under consideration as treatments for diarrhoea and other intestinal disorders. We investigated the gastrointestinal consequences of selective PYY or NPY ablation on mucosal ion transport, smooth muscle activity and transit u...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2011.01401.x
更新日期:2011-09-01 00:00:00