Des-aspartate-angiotensin I causes specific release of PGE2 and PGI2 in HUVEC via the angiotensin AT1 receptor and biased agonism.


:DAA-I (des-aspartate-angiotensin I), an endogenous angiotensin, had been shown earlier to ameliorate animal models of cardiovascular diseases via the angiotensin AT1 receptor and prostaglandins. The present study investigated further the action of DAA-I on the release of PGE2, PGI2, PGF2α and TXA2 in HUVEC. 10(-11)-10(-8)M DAA-I and 15min incubation specifically released PGE2 and PGI2. The release was inhibited by losartan and indomethacin but not by PD123319 and NS398 indicating that the angiotensin AT1 receptor and COX-1 mediate the release. At concentrations higher than 10(-7)M, DAA-I mimics the action of angiotensin II by releasing TXA2 but had no effect on the production of PGF2α. At similar concentrations and 4h incubation, DAA-I increased the release of the 4 prostaglandins via the angiotensin AT1 receptor and COX-2, again mimicking the action of angiotensin II. HUVEC that were preincubated with DAA-I or angiotensin II, released similar profiles of prostaglandins when incubated with arachidonic acid after the angiotensin had been washed off. We postulate that the internalized DAA-I/receptor complex remains active and mediates the conversion of arachidonic acid to the respective prostaglandins. The release of PGE2 and PGI2 via the angiotensin AT1 receptor and COX-1 is a novel specific action of DAA-I and is likely responsible for its beneficial effects seen in earlier studies. This specific action is definable as a biased agonism of the angiotensin AT1 receptor, which identifies DAA-I as a novel biased agonist and potential therapeutic that is able to produce specific prostaglandins at nanomolar concentrations.


Eur J Pharmacol


Wen Q,Lee KO,Sim SZ,Xu XG,Sim MK




Has Abstract


2015-12-05 00:00:00












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    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: Konturek SJ,Brzozowski T,Majka J,Pytko-Polonczyk J,Stachura J

    更新日期:1993-08-03 00:00:00

  • Nordihydroguaiaretic acid inhibits transforming growth factor beta type 1 receptor activity and downstream signaling.

    abstract::It has been well documented that nordihydroguaiaretic acid (NDGA), a phenolic lignan isolated from the creosote bush, Larrea tridentate, has anti-cancer activity in vitro and in vivo. Several mechanisms have been identified that could contribute to these actions, as NDGA directly inhibits metabolic enzymes and recepto...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: Li F,Pham JD,Anderson MO,Youngren JF

    更新日期:2009-08-15 00:00:00

  • Effects of guinea pig neurotensin ([Ser7]neurotensin) on gastrointestinal smooth muscle.

    abstract::Guinea pig neurotensin differs from other mammalian neurotensin by the substitution of proline by serine at position 7. [Ser7]neurotensin produced a concentration-dependent contraction of the guinea pig oesophagus and rat fundus, a biphasic effect (initial relaxation followed by more sustained contraction) on the guin...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: Katsoulis S,Conlon JM

    更新日期:1987-08-21 00:00:00

  • Localization of cholinergic neurons involved in the cardiovascular response to intrathecal injection of carbachol.

    abstract::Recent studies in this laboratory have demonstrated the ability of acetylcholine receptor agonists to produce systemic arterial pressor responses through stimulation of spinal muscarinic receptors. In urethane-anesthetized rats a new surgical procedure was employed to permit microinjection of drugs into the cerebrospi...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: Feldman DS,Buccafusco JJ

    更新日期:1993-12-21 00:00:00

  • Characterization of a novel muscarinic receptor agonist, YM796: comparison with cholinesterase inhibitors in in vivo pharmacological studies.

    abstract::Previous reports have shown that (+/-)-YM796 (2,8-dimethyl-3-methylene-1-oxa-8-azaspiro[4.5]decane) exhibits M1 agonistic activity and ameliorates cognitive impairment, and that the (-)-S isomer is active in in vitro studies. We report here the characterization of the (-)-S isomer, YM796 ((-)-(S)-2,8-dimethyl-3-methyl...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: Wanibuchi F,Nishida T,Yamashita H,Hidaka K,Koshiya K,Tsukamoto S,Usuda S

    更新日期:1994-11-24 00:00:00

  • Blockade of human IsK channels expressed in Xenopus oocytes by the novel class III antiarrhythmic NE-10064.

    abstract::cRNA encoding the human IsK protein was injected into Xenopus oocytes and the expressed channels were investigated using the two-microelectrode voltage-clamp method. The novel class III antiarrhythmic NE-10064 (1-[[[5-(4-chlorophenyl)-2-furanyl]methylene]-amino]-3- [4-(4-methyl-1-piperazinyl)-butyl]-2,4-imidazolidined...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: Busch AE,Herzer T,Takumi T,Krippeit-Drews P,Waldegger S,Lang F

    更新日期:1994-10-13 00:00:00

  • Mechanism of inhibition of platelet aggregation by rutaecarpine, an alkaloid isolated from Evodia rutaecarpa.

    abstract::In this study, rutaecarpine was tested for its antiplatelet activities in human platelet-rich plasma. In human platelet-rich plasma, rutaecarpine (40-200 microM) inhibited aggregation stimulated by a variety of agonists (i.e., collagen, ADP, adrenaline and arachidonic acid). The antiplatelet activity of rutaecarpine (...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: Sheu JR,Hung WC,Lee YM,Yen MH

    更新日期:1996-12-30 00:00:00

  • Pleiotropic protective effects of Vitamin D against high fat diet-induced metabolic syndrome in rats: One for all.

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    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: Mostafa DK,Nasra RA,Zahran N,Ghoneim MT

    更新日期:2016-12-05 00:00:00

  • Specific effects of chronic phenobarbital administration on high- and low-affinity benzodiazepine receptors in mouse cerebellum and forebrain.

    abstract::Characteristics of [3H]flunitrazepam ([3H]FLU) binding to cortical and cerebellar membrane receptors were examined following chronic (six days) administration of phenobarbital (PB) to C57B1 mice. Following PB treatment, the number of [3H]FLU binding sites (Bmax) was significantly reduced in both cerebral cortex and in...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: Liljequist S,Garrett KM,Tabakoff B

    更新日期:1984-08-17 00:00:00

  • Effect of acute treatment with YM992 on extracellular norepinephrine levels in the rat frontal cortex.

    abstract::The effects of acute treatment with (S)-2-[[(7-fluoroindan-4-yl)oxy]methyl]morpholine monohydrochloride (YM992), venlafaxine, fluoxetine and citalopram on extracellular norepinephrine levels were examined in the rat frontal cortex by in vivo microdialysis. YM992 (3, 10, 30 mg/kg, i.p.) dose-dependently increased extra...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: Hatanaka K,Yatsugi S,Yamaguchi T

    更新日期:2000-04-21 00:00:00

  • Pharmacological and histochemical evidence for P2X receptors in human umbilical vessels.

    abstract::The presence of P2X purinoceptors in human umbilical vessels were studied with organ bath recording, radioligand binding assays, autoradiography, and immunohistochemistry. In isolated umbilical arteries and veins from normal term pregnancy, both ATP and alpha,beta-methylene ATP caused concentration-dependent contracti...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: Bo X,Sexton A,Xiang Z,Nori SL,Burnstock G

    更新日期:1998-07-17 00:00:00

  • The thromboxane A2/prostaglandin endoperoxide receptor antagonist activity of CV-4151, a thromboxane A2 synthetase inhibitor.

    abstract::The thromboxane A2/prostaglandin endoperoxide (TXA2/PGH2) receptor antagonist activity of CV-4151, a potent TXA2 synthetase inhibitor, was examined. CV-4151 inhibited guinea pig and human platelet aggregation induced by U-44069 with IC50 values of 1.2 +/- 0.3 X 10(-5) and 1.9 +/- 0.4 X 10(-5) M, respectively, and inhi...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: Imura Y,Terashita Z,Shibouta Y,Nishikawa K

    更新日期:1988-03-15 00:00:00

  • Telmisartan, an angiotensin II type 1 receptor antagonist, attenuates T-type Ca2+ channel expression in neonatal rat cardiomyocytes.

    abstract::Recently, it has been revealed that angiotensin II type 1 receptor (AT(1)) antagonists act as antiarrhythmic agents and that the T-type Ca2+ channel plays an important role in arrhythmia. However, it remains unclear how the T-type Ca2+ channel expression system is involved in angiotensin II-mediated arrhythmogenesis i...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: Morishima M,Wang Y,Akiyoshi Y,Miyamoto S,Ono K

    更新日期:2009-05-01 00:00:00

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    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: Robich MP,Osipov RM,Chu LM,Han Y,Feng J,Nezafat R,Clements RT,Manning WJ,Sellke FW

    更新日期:2011-08-16 00:00:00

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    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: McKendrick G,Sharma S,Sun D,Randall PA,Graziane NM

    更新日期:2020-12-15 00:00:00

  • Phytochemical compounds targeting on Nrf2 for chemoprevention in colorectal cancer.

    abstract::Colorectal cancer (CRC) has become one of the major factors of tumor-related morbidity and mortality in the world because of its poor prognosis and consequences of metastatic spread. Currently, chemoprevention has been considered as a way of preventing cancer who takes advantage of plant phytochemicals and synthetic c...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章,评审


    authors: Zhu Y,Yang Q,Liu H,Song Z,Chen W

    更新日期:2020-11-15 00:00:00

  • The mode of vasoinhibitory action of a pyridazione derivative (MCI-154), a new cardiotonic agent, on contractile responses induced by alpha-adrenoceptor agonists and 45Ca influx in isolated vascular smooth muscles.

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    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: Shibata S,Satake N,Hester RK,Kurahashi K,Ito M

    更新日期:1988-01-12 00:00:00

  • In vivo and in vitro study of the influence of the anticholinesterase drug galantamine on motor and evacuative functions of rat gastrointestinal tract.

    abstract::Galantamine is efficacious for vascular dementia and Alzheimer's disease. Its application leads to some negative gastrointestinal side effects. The present study observes galantamine-induced influence on gastrointestinal motility of rats and its effects on isolated gastrointestinal smooth muscles. The gastrointestinal...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: Turiiski VI,Krustev AD,Sirakov VN,Getova DP

    更新日期:2004-09-13 00:00:00

  • Role of delta-opioid receptors in mediating the aversive stimulus effects of morphine withdrawal in the rat.

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    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: Funada M,Schutz CG,Shippenberg TS

    更新日期:1996-04-04 00:00:00

  • Pharmacological studies on the NOP and opioid receptor agonist PWT2-[Dmt1]N/OFQ(1-13).

    abstract::An innovative chemical strategy named peptide welding technology (PWT) has been developed for the facile synthesis of tetrabranched peptides. [Dmt1]N/OFQ(1-13)-NH2 acts as a universal agonist for nociceptin/orphanin FQ (N/OFQ) and classical opioid receptors. The present study investigated the pharmacological profile o...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: Cerlesi MC,Ding H,Bird MF,Kiguchi N,Ferrari F,Malfacini D,Rizzi A,Ruzza C,Lambert DG,Ko MC,Calo G,Guerrini R

    更新日期:2017-01-05 00:00:00

  • Electroencephalographic study of SR 95103, a GABAA antagonist: interaction with inhibitory amino acids and muscimol.

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    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: Santucci V,Fournier M,Chambon JP,Biziere K

    更新日期:1985-08-15 00:00:00

  • Coronary response to diadenosine tetraphosphate after ischemia-reperfusion in the isolated rat heart.

    abstract::Diadenosine tetraphosphate (AP4A) is a vasoactive mediator that may be released from platelet granules and that may reach higher plasma concentrations during coronary ischemia-reperfusion. The objective of this study was to analyze its coronary effects in such conditions. To this, rat hearts were perfused in a Langend...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: García-Villalón AL,Fernández N,Monge L,Diéguez G

    更新日期:2011-06-25 00:00:00

  • Negative effect of serotonin-norepinephrine reuptake inhibitor therapy on rat bone tissue after orchidectomy.

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    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: Fekete S,Simko J,Mzik M,Karesova I,Zivna H,Zivny P,Pavliková L,Palicka V

    更新日期:2015-08-15 00:00:00

  • Effect of chronic moderate ethanol consumption on heart brain natriuretic peptide.

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    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: Guillaume P,Jankowski M,Gutkowska J,Gianoulakis C

    更新日期:1996-11-28 00:00:00

  • In vitro binding of the very potent and selective D-2 dopamine agonist, [3H]N-0437 to calf caudate membranes.

    abstract::N-0437, a non-catecholic aminotetralin has recently been described as a very potent and selective dopamine D-2 agonist. In this study the in vitro binding of [3H]N-0437 (specific activity 80.6 Ci/mmol) to calf caudate membranes is described. It was found that [3H]N-0437 binds with a high affinity (KD = 0.17 nM) and a ...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: Van der Weide J,De Vries JB,Tepper PG,Horn AS

    更新日期:1987-02-10 00:00:00

  • Oral administration of quercetin inhibits bone loss in rat model of diabetic osteopenia.

    abstract::Diabetic osteopenia can result in an increased incidence of bone fracture and a delay in fracture healing. Quercetin, one of the most widely distributed flavonoids in plants, possesses antioxidant property and beneficial effect on osteoporosis in ovariectomized mice. All these properties make quercetin a potential can...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: Liang W,Luo Z,Ge S,Li M,Du J,Yang M,Yan M,Ye Z,Luo Z

    更新日期:2011-11-16 00:00:00

  • Nitrate tolerance and aging in isolated rat aorta.

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    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: Unger P,Berkenboom G,Brékine D,Fontaine J

    更新日期:1993-08-02 00:00:00

  • The adenosine A1 receptor agonist N6-cyclopentyladenosine blocks the disruptive effect of phencyclidine on prepulse inhibition of the acoustic startle response in the rat.

    abstract::Systemic administration of the NMDA receptor antagonist phencyclidine (PCP; 4 mg/kg) produced a profound reduction in prepulse inhibition of the acoustic startle response in rats. Pre-treatment with the selective adenosine A1 receptor agonist N6-cyclopentyladenosine (CPA) blocked (0.5 mg/kg) or attenuated (0.1 and 0.2...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: Sills TL,Azampanah A,Fletcher PJ

    更新日期:1999-03-26 00:00:00

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    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: Abe Y,Kitada Y,Narimatsu A,Tobe A

    更新日期:1991-01-10 00:00:00

  • Effect of amlodipine on mouse renal interstitial fibrosis.

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    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: Honma S,Nakamura K,Shinohara M,Mitazaki S,Abe S,Yoshida M

    更新日期:2016-06-05 00:00:00