当前位置： SCI文献检索 > EUROPEAN JOURNAL OF PHARMACOLOGY期刊下所有文献 > In vivo and in vitro evaluation of novel μ-opioid receptor agonist compounds.

In vivo and in vitro evaluation of novel μ-opioid receptor agonist compounds.

Abstract：

:Opioids are the most effective and widely used drugs for pain treatment. Morphine is an archetypal opioid and is an opioid receptor agonist. Unfortunately, the clinical usefulness of morphine is limited by adverse effects such as analgesic tolerance and addiction. Therefore, it is important to study the development of novel opioid agonists as part of pain control. The analgesic effects of opioids are mediated by three opioid receptors, namely opioid μ-, δ-, and κ-receptors. They belong to the G protein-coupled receptor superfamily and are coupled to Gi proteins. In the present study, we developed a ligand screening system to identify novel opioid μ-receptor agonists that measures [(35)S]GTPγS binding to cell membrane fractions prepared from the fat body of transgenic silkworms expressing μ-receptor-Gi1α fusion protein. We screened the RIKEN Natural Products Depository (NPDepo) chemical library, which contains 5848 compounds, and analogs of hit compounds. We successfully identified a novel, structurally unique compound, that we named GUM1, with agonist activity for the opioid μ-receptor (EC50 of 1.2 µM). The Plantar Test (Hargreaves' Method) demonstrated that subcutaneous injection of 3mg/kg of GUM1 into wild-type rats significantly extended latency time. This extension was also observed in a rat model of morphine tolerance and was inhibited by pre-treatment of naloxone. The unique molecular skeleton of GUM1 makes it an attractive molecule for further ligand-opioid receptor binding studies.

journal_name

Eur J Pharmacol

journal_title

European journal of pharmacology

authors

Nikaido Y,Kurosawa A,Saikawa H,Kuroiwa S,Suzuki C,Kuwabara N,Hoshino H,Obata H,Saito S,Saito T,Osada H,Kobayashi I,Sezutsu H,Takeda S

doi

10.1016/j.ejphar.2015.10.025

subject

Has Abstract

pub_date

2015-11-15 00:00:00

pages

193-200

eissn

0014-2999

issn

1879-0712

pii

S0014-2999(15)30306-X

journal_volume

767

pub_type

杂志文章

相关文献

EUROPEAN JOURNAL OF PHARMACOLOGY文献大全
  • Transfection of PDCD5 sensitizes colorectal cancer cells to cisplatin-induced apoptosis in vitro and in vivo.

    abstract：:This study was purposed to explore the mechanism of augmenting apoptosis-inducing effects of cisplatin on colorectal cancer SW480 cells by stable transfection of Programmed Cell Death 5 (PDCD5) gene, both in vitro and in vivo. The expression level of PDCD5 of SW480 cells stably transfected with PDCD5 (SW480/PDCD5) and...

    journal_title：European journal of pharmacology

    pub_type： 杂志文章

    doi：10.1016/j.ejphar.2010.09.040

    authors： Yin A,Jiang Y,Zhang X,Zhao J,Luo H

    更新日期：2010-12-15 00:00:00

  • Facilitation of 8-OHDPAT-induced forepaw treading of rats by the 5-HT2 agonist DOI.

    abstract：:The potency of the serotonin 1A (5-HT1A) agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OHDPAT), to induce forepaw treading was increased 20-fold after co-treatment with the 5-HT2 agonist, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI). DOI induced head twitches which were inhibited by 8-OHDPAT. The putative ...

    journal_title：European journal of pharmacology

    pub_type： 杂志文章

    doi：10.1016/0014-2999(89)90178-7

    authors： Arnt J,Hyttel J

    更新日期：1989-02-14 00:00:00

  • Allosteric interactions of three muscarine antagonists at bovine tracheal smooth muscle and cardiac M2 receptors.

    abstract：:The kinetics of [3H]dexetimide dissociation from muscarine receptors in bovine cardiac left ventricular and tracheal smooth muscle membranes were studied in the absence and presence of three muscarine antagonists. It was found that [3H]dexetimide dissociation from cardiac muscarine receptors was monophasic and very fa...

    journal_title：European journal of pharmacology

    pub_type： 杂志文章

    doi：10.1016/0922-4106(89)90045-x

    authors： Roffel AF,Elzinga CR,Meurs H,Zaagsma J

    更新日期：1989-03-07 00:00:00

  • Cyclic 3',5'-adenosine monophosphate and bronchial tone.

    abstract：:The present studies demonstrate that adenylate cyclase and cyclic 3',5'-adenosine monophosphate (cAMP)-phosphodiesterase activities in dog bronchus are comparable to those found in other smooth muscle preparations. Catecholamines, in the order isoproterenol greater than epinephrine greater than norepinephrine, increas...

    journal_title：European journal of pharmacology

    pub_type： 杂志文章

    doi：10.1016/0014-2999(77)90368-5

    authors： Triner L,Vulliemoz Y,Verosky M

    更新日期：1977-01-07 00:00:00

  • Amygdalar neuropeptide Y Y1 receptors mediate the anxiolytic-like actions of neuropeptide Y in the social interaction test.

    abstract：:The effects of intra-amygdalar neuropeptide Y infusions were assessed in rats using the social interaction test. Neuropeptide Y administered into the central nucleus of the amygdala did not alter behavior, while injections into the basolateral nucleus of the amygdala produced an increased social interaction time. Furt...

    journal_title：European journal of pharmacology

    pub_type： 杂志文章

    doi：10.1016/s0014-2999(99)00018-7

    authors： Sajdyk TJ,Vandergriff MG,Gehlert DR

    更新日期：1999-03-05 00:00:00

  • Atypical effect of dopamine in modulating the functional inhibition of NMDA receptors of cultured retina cells.

    abstract：:Cultured retina cells released accumulated [3H]GABA (gamma-aminobutyric acid) when stimulated by L-glutamate, N-methyl-D-aspartate (NMDA) and kainate. In the absence of Mg2+, dopamine at 200 microM (IC50 60 microM), inhibited in more than 50% the release of [3H]GABA induced by L-glutamate and NMDA, but not by kainate....

    journal_title：European journal of pharmacology

    pub_type： 杂志文章

    doi：10.1016/s0014-2999(97)01522-7

    authors： Do Nascimento JL,Kubrusly RC,Reis RA,De Mello MC,De Mello FG

    更新日期：1998-02-05 00:00:00

  • Regulatory role of the dopamine and norepinephrine transporters in pentylenetetrazol-kindled mice: association with effect of antidepressants.

    abstract：:In clinical practice, patients with epilepsy are frequently associated with psychiatric disorders, including cognitive impairment, depression, and attention deficit hyperactivity disorder. In fact, patients with epilepsy often take centrally acting drugs, such as antidepressants and anxiolytics; however, it remains un...

    journal_title：European journal of pharmacology

    pub_type： 杂志文章

    doi：10.1016/j.ejphar.2011.10.017

    authors： Takechi K,Suemaru K,Kawasaki H,Araki H

    更新日期：2011-12-30 00:00:00

  • Expression of purinergic P2Y receptor subtypes by INS-1 insulinoma beta-cells: a molecular and binding characterization.

    abstract：:Purinergic P2Y-receptor agonists amplify glucose-induced insulin secretion from pancreatic beta-cells, thus offering new opportunities for the treatment of type 2 diabetes. However, little is known about which subtypes of purinergic P2Y receptors are expressed in these cells. The INS-1 beta-cell line is used as a mode...

    journal_title：European journal of pharmacology

    pub_type： 杂志文章

    doi：10.1016/j.ejphar.2007.04.012

    authors： Lugo-Garcia L,Filhol R,Lajoix AD,Gross R,Petit P,Vignon J

    更新日期：2007-07-30 00:00:00

  • Downregulation of estrogen-related receptor alpha inhibits human cutaneous squamous cell carcinoma cell proliferation and migration by regulating EMT via fibronectin and STAT3 signaling pathways.

    abstract：:Estrogen-related receptor alpha (ERRα), one of orphan nuclear receptors, has been recently revealed as an oncogenic regulator in a variety of cancers. However, the linking gain of ERRα expression and cancer progression in cutaneous squamous cell carcinoma (cSCC) is largely unknown. Here, we showed that the mRNA and pr...

    journal_title：European journal of pharmacology

    pub_type： 杂志文章

    doi：10.1016/j.ejphar.2018.02.025

    authors： Chen H,Pan J,Zhang L,Chen L,Qi H,Zhong M,Shi X,Du J,Li Q

    更新日期：2018-04-15 00:00:00

  • Raloxifene promotes adipocyte differentiation of 3T3-L1 cells.

    abstract：:To explore the possibility that raloxifene might influence an adipocyte differentiation and lipogenesis, we studied the effects of raloxifene on the expression of adiponectin and other peroxisome proliferator-activated receptor gamma targeting genes using the 3T3-L1 adipocytes. With standard adipogenic inducers, we ad...

    journal_title：European journal of pharmacology

    pub_type： 杂志文章

    doi：10.1016/j.ejphar.2006.03.033

    authors： Murase Y,Kobayashi J,Nohara A,Asano A,Yamaaki N,Suzuki K,Sato H,Mabuchi H

    更新日期：2006-05-24 00:00:00

  • Increase in P-glycoprotein levels in the blood-brain barrier of partial portal vein ligation /chronic hyperammonemia rats is medicated by ammonia/reactive oxygen species/ERK1/2 activation: In vitro and in vivo studies.

    abstract：:Liver failure altered P-glycoprotein (P-gp) function and expression at blood-brain barrier (BBB), partly owing to hyperammonemia. We aimed to examine the effects of partial portal vein ligation (PVL) plus chronic hyperammonemia (CHA) on P-gp function and expression at rat BBB. Experimental rats included sham-operation...

    journal_title：European journal of pharmacology

    pub_type： 杂志文章

    doi：10.1016/j.ejphar.2019.01.005

    authors： Zhou Y,Zhou J,Li P,Xie Q,Sun B,Li Y,Chen Y,Zhao K,Yang T,Zhu L,Xu J,Liu X,Liu L

    更新日期：2019-03-05 00:00:00

  • Antidepressants: past, present and future.

    abstract：:Since the discovery of first antidepressants in mid-1950's, the field has been intensively studied. Several new classes of compounds emerged and several hypotheses on the mechanism of their action were proposed. The novel antidepressants are either selective and reversible monoamine oxidase inhibitors, (e.g., moclobem...

    journal_title：European journal of pharmacology

    pub_type： 杂志文章,评审

    doi：10.1016/s0014-2999(00)00565-3

    authors： Vetulani J,Nalepa I

    更新日期：2000-09-29 00:00:00

  • Methamphetamine selectively alters brain glutathione.

    abstract：:As methamphetamine-induced neurotoxicity has been proposed to involve oxidative stress, reduced and oxidized glutathione (GSH and GSSG, respectively), vitamin E and ascorbate were measured in the striata of rats killed 2 or 24 h after a neurotoxic regimen of methamphetamine. At 2 h, methamphetamine increased GSH and G...

    journal_title：European journal of pharmacology

    pub_type： 杂志文章

    doi：10.1016/s0014-2999(00)00392-7

    authors： Harold C,Wallace T,Friedman R,Gudelsky G,Yamamoto B

    更新日期：2000-07-14 00:00:00

  • Role of gap junction in the expression of morphine-induced antinociception.

    abstract：:The present study was undertaken to investigate whether gap junctional communication could be involved in morphine-induced antinociceptive response using blockers of the gap junctional channel, carbenoxolone and Gap27. Intrathecal pretreatment with either carbenoxolone or Gap27 caused a dose-dependent attenuation of m...

    journal_title：European journal of pharmacology

    pub_type： 杂志文章

    doi：10.1016/j.ejphar.2006.01.038

    authors： Suzuki M,Narita M,Nakamura A,Suzuki T

    更新日期：2006-03-27 00:00:00

  • Protein kinase C activation and anti-amnesic effect of acetyl-L-carnitine: in vitro and in vivo studies.

    abstract：:Drugs belonging to different chemical classes having the ability to improve behavioral performance in animal learning and memory tests may share the common ability to stimulate protein kinase C activity in rat brain cortex. In vitro acetyl-L-carnitine (100 nM) promoted in rat brain cortex slices a significant increase...

    journal_title：European journal of pharmacology

    pub_type： 杂志文章

    doi：10.1016/0014-2999(94)90216-x

    authors： Pascale A,Milano S,Corsico N,Lucchi L,Battaini F,Martelli EA,Trabucchi M,Govoni S

    更新日期：1994-11-14 00:00:00

  • Epinephrine as a potent releaser of immunoreactive beta-endorphin in rats.

    abstract：:The intravenous infusion of catecholamines to rats induced a dose dependent increase of immunoreactive beta-endorphin (beta-Endi) in plasma. The ED50 values of 1-epinephrine and 1-isoproterenol were 110 and 100 ng/kg X min respectively. 1-Propranolol, but not d-propranolol prevented the effect of 1-epinephrine. Infusi...

    journal_title：European journal of pharmacology

    pub_type： 杂志文章

    doi：10.1016/0014-2999(81)90303-4

    authors： Berkenbosch F,Vermes I,Tilders FJ

    更新日期：1981-06-10 00:00:00

  • Animal models of rheumatoid arthritis: How informative are they?

    abstract：:Animal models of arthritis are widely used to de-convolute disease pathways and to identify novel drug targets and therapeutic approaches. However, the high attrition rates of drugs in Phase II/III rates means that a relatively small number of drugs reach the market, despite showing efficacy in pre-clinical models. Th...

    journal_title：European journal of pharmacology

    pub_type： 杂志文章,评审

    doi：10.1016/j.ejphar.2015.03.047

    authors： McNamee K,Williams R,Seed M

    更新日期：2015-07-15 00:00:00

  • Ca2+ channel blockers prevent seizures induced by a class of K+ channel inhibitors.

    abstract：:Intracerebroventricular injection into rats of mast-cell degranulating peptide (MCD), dendrotoxin I (DTXI) and 4-aminopyridine (4-AP), three blockers of a subclass of K+ channels, elicited epileptiform wave bursts and convulsions. Three different types of L-type Ca2+ channel inhibitors (+)PN 200-110, a 1,4-dihydropyri...

    journal_title：European journal of pharmacology

    pub_type： 杂志文章

    doi：10.1016/0014-2999(89)90669-9

    authors： Gandolfo G,Gottesmann C,Bidard JN,Lazdunski M

    更新日期：1989-01-24 00:00:00

  • Enhanced endothelial nitric oxide activity contributes to the reduced responsiveness of vascular alpha1-adrenoceptors following aortic barodenervation.

    abstract：:We have recently shown that short-term aortic barodenervation diminishes constrictor responses to activation of alpha1-adrenoceptors in rat aortic smooth muscle. This study investigated the potential role of vascular endothelium and its derived vasoactive substances, nitric oxide and prostaglandins, in the reduced alp...

    journal_title：European journal of pharmacology

    pub_type： 杂志文章

    doi：10.1016/s0014-2999(97)01283-1

    authors： El-Mas MM,Daabees TT,El-Gowelli HM,Abdel-Galil AG

    更新日期：1997-10-22 00:00:00

  • Enhanced effect of neuropeptide Y on food intake caused by blockade of the V(1A) vasopressin receptor.

    abstract：:Food intake is regulated by various factors such as neuropeptide Y. Neuropeptide Y potently induces an increase in food intake, and simultaneously stimulates arginine-vasopressin (AVP) secretion in the brain. Recently, we reported that V(1A) vasopressin receptor-deficient (V(1A)R(-/-)) mice exhibited altered daily foo...

    journal_title：European journal of pharmacology

    pub_type： 杂志文章

    doi：10.1016/j.ejphar.2009.09.017

    authors： Aoyagi T,Kusakawa S,Sanbe A,Hiroyama M,Fujiwara Y,Yamauchi J,Tanoue A

    更新日期：2009-11-10 00:00:00

  • L-cysteine augments the vasorelaxation induced by sodium nitrite and SIN-1 but not that due to acetylcholine.

    abstract：:The effects of 1 mM L-cysteine on sodium nitrite-, 3-morpholinosydnonimine (SIN-1)- and acetylcholine-induced relaxation and cyclic GMP accumulation were studied in isolated noradrenaline-precontracted rat mesenteric arterial rings. L-Cysteine augmented the relaxation and cyclic GMP increase induced by sodium nitrate ...

    journal_title：European journal of pharmacology

    pub_type： 杂志文章

    doi：10.1016/0014-2999(92)90133-o

    authors： Arvola P,Pörsti I,Vuorinen P,Huhtala H,Metsä-Ketelä T,Vapaatalo H

    更新日期：1992-04-22 00:00:00

  • Delineation of the protective action of zinc sulfate on ulcerative colitis in rats.

    abstract：:The protective action of zinc compounds in Crohn's disease-like inflammatory bowel disease in animals has been shown. A similar action of zinc sulfate on ulcerative colitis has not been defined. The present study aimed to delineate the protective action of zinc sulfate and the pathogenic mechanisms of 2,4-dinitrobenze...

    journal_title：European journal of pharmacology

    pub_type： 杂志文章

    doi：10.1016/s0014-2999(02)01592-3

    authors： Luk HH,Ko JK,Fung HS,Cho CH

    更新日期：2002-05-17 00:00:00

  • N-methyl-D-aspartate and alpha 2-adrenergic mechanisms are involved in the depressant action of flupirtine on spinal reflexes in rats.

    abstract：:In urethane-chloralose anesthetised rats the muscle relaxant activity of flupirtine was investigated on the monosynaptic Hoffmann reflex recorded from plantar foot muscles and on the polysynaptic flexor reflex recorded from tibialis muscle. Intraperitoneal (i.p.; 2.5-25 mumol/kg) and intrathecal (i.t.; 33-330 nmol) ad...

    journal_title：European journal of pharmacology

    pub_type： 杂志文章

    doi：10.1016/0014-2999(95)00043-k

    authors： Schwarz M,Schmitt T,Pergande G,Block F

    更新日期：1995-04-04 00:00:00

  • Spinal antinociceptive effects of AA501, a novel chimeric peptide with opioid receptor agonist and tachykinin receptor antagonist moieties.

    abstract：:The use of "multimodal" combination analgesic therapies or novel single molecules possessing multiple analgesic targets is becoming increasingly attractive. In previous experiments we showed that a substance P antagonist injected intrathecally potentiated the antinociceptive effects of potent opioid receptor agonist, ...

    journal_title：European journal of pharmacology

    pub_type： 杂志文章

    doi：10.1016/j.ejphar.2004.02.023

    authors： Bonney IM,Foran SE,Marchand JE,Lipkowski AW,Carr DB

    更新日期：2004-03-19 00:00:00

  • Assay development of inducible human renal phosphate transporter Npt2A (SLC34A1) in Flp-In-Trex-HEK293 cells.

    abstract：:Hyperphosphatemia is associated with severe decline of renal function in chronic kidney disease and elevates cardiovascular mortality. Type II sodium dependent phosphate transporter 2A (Npt2A) plays a major role in renal phosphate reabsorption and could be explored as a target for anti-hyperphosphatemia therapy. Human...

    journal_title：European journal of pharmacology

    pub_type： 杂志文章

    doi：10.1016/j.ejphar.2013.09.005

    authors： Wu H,Mao C,Duenstl G,Su W,Qian S

    更新日期：2013-12-05 00:00:00

  • Amitriptyline, desipramine, cyproheptadine and carbamazepine, in concentrations used therapeutically, reduce kainate- and N-methyl-D-aspartate-induced intracellular Ca2+ levels in neuronal culture.

    abstract：:The glutamate receptor agonists, kainate and N-methyl-D-aspartate (NMDA) result in the elevation of intracellular calcium levels ([Ca2+]i) in primary cultures of cerebellar granule neurons. Several tricyclic antidepressants (TCAs), amitriptyline (0.5-1 microM), desipramine (1 microM) and doxepine (1 microM) partially ...

    journal_title：European journal of pharmacology

    pub_type： 杂志文章

    doi：10.1016/0014-2999(92)90579-s

    authors： Cai Z,McCaslin PP

    更新日期：1992-08-14 00:00:00

  • Celastrol attenuates symptoms of preeclampsia in rats by inhibiting matrix metalloproteinase-9.

    abstract：:Preeclampsia is reported in pregnant women around the world and often causes maternal/fetal mortality and morbidity. In the current study, we assessed the efficacy of celastrol on a rat preeclampsia model induced by Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME). Pregnant rats were administered L-NAME to esta...

    journal_title：European journal of pharmacology

    pub_type： 杂志文章

    doi：10.1016/j.ejphar.2018.04.025

    authors： Xiao S,Zhang M,He Z,Wang D

    更新日期：2018-07-05 00:00:00

  • Homologous tachyphylaxis to bradykinin and its interference with allergic pleurisy in actively sensitized rats.

    abstract：:After recovery from a first intraplantar or intrathoracic stimulation with bradykinin, repeated daily provocation with this peptide resulted in a progressive loss of its ability to cause paw or pleural oedema, reaching 0-20% of the control within seven and four consecutive provocations, respectively. The phenomenon wa...

    journal_title：European journal of pharmacology

    pub_type： 杂志文章

    doi：10.1016/0014-2999(92)90011-r

    authors： Martins MA,Pasquale CP,Bozza PT,Silva PM,Faria Neto HC,COrdeiro RS

    更新日期：1992-09-10 00:00:00

  • Interactive effect of histamine and prostaglandin D2 on nasal allergic symptoms in rats.

    abstract：:This study was undertaken to investigate the interactive effect of histamine and prostaglandin D(2) in nasal allergic symptoms in rats. The intranasal application of histamine at doses lower than 10 mumol/site caused no sneezing or nasal rubbing. In addition, prostaglandin D(2) also showed no significant increase in t...

    journal_title：European journal of pharmacology

    pub_type： 杂志文章

    doi：10.1016/j.ejphar.2006.09.060

    authors： Rahman A,Inoue T,Ago J,Ishikawa T,Kamei C

    更新日期：2007-01-12 00:00:00

  • Effect of quercetin, flavonoids and alpha-tocopherol, an antioxidant vitamin, on experimental reflux oesophagitis in rats.

    abstract：:Protective effect of quercetin and alpha-tocopherol on experimental reflux oesophagitis in rats was investigated. Rats received quercetin, (100 mg/kg), alpha-tocopherol (16 mg/kg), omeprazole (30 mg/kg) given at 1 h prior to surgery. Quercetin and alpha-tocopherol significantly inhibited the oesophagitis index to 1.33...

    journal_title：European journal of pharmacology

    pub_type： 杂志文章

    doi：10.1016/j.ejphar.2008.04.062

    authors： Rao CV,Vijayakumar M

    更新日期：2008-07-28 00:00:00