Phorbol ester regulates stimulatory and inhibitory pathways of the hormone-sensitive adenylate cyclase system in rat reticulocytes.


:Treatment of rat reticulocytes with tetradecanoyl phorbol acetate (TPA), a tumor-promoting phorbol ester which activates protein kinase C, resulted in an about 50% decrease in the stimulation of adenylate cyclase activity by a subsequent challenge with a beta-adrenoceptor agonist. This phenomenon mimics agonist-induced desensitization. This decline is due to a reduction in the Vmax of the adenylate cyclase system rather than to a change in affinity to the agonist. The beta-adrenoceptor number was not changed while the KD for an agonist but not for an antagonist was increased by TPA treatment. Prostaglandin E1 (PGE1) plus GTP, NaF plus AlCl3, and guanylyl-5'-imidodiphosphate (GppNHp) regulated adenylate cyclase activity in a biphasic manner, i.e. stimulation at lower concentrations and inhibition at higher concentrations. The same treatment also caused a dose- and time-dependent reduction of the inhibitory phase of the PGE1/GTP action but did not affect the inhibitory phase of GppNHp and NaF/AlCl3 actions. Pertussis toxin (IAP) treatment caused a reduction of the inhibitory phase of PGE1/GTP action similar to that caused by TPA treatment. No synergistic effect was observed when the cells were treated with TPA and IAP simultaneously. These results suggest that TPA treatment impairs the coupling between PGE1 receptor and Gi rather than enhances that between PGE1 receptor and Gs. Protein kinase C was involved in the regulation of hormone-sensitive adenylate cyclase, the beta-agonist-induced stimulatory pathway and the PGE1-induced inhibitory pathway in rat reticulocytes, since other phorbol esters and diacylglycerol, which activate this kinase, caused the same response.(ABSTRACT TRUNCATED AT 250 WORDS)


Eur J Pharmacol


Yamashita A,Kurokawa T,Une Y,Ishibashi S




Has Abstract


1988-07-07 00:00:00














  • Improvement of postischemic contractile dysfunction of dog heart by MCI-154, a novel cardiotonic agent.

    abstract::The effects of MCI-154, a cardiotonic agent which has direct effects on cardiac myofilaments, on postischemic contractile dysfunction were studied in dog heart subjected to a 30-min occlusion of the left anterior descending coronary artery followed by reperfusion, and compared with the effects of milrinone and dobutam...

    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

  • Enhanced vasoconstriction to α1-adrenoceptor stimulation during cooling in mouse cutaneous plantar arteries.

    abstract::Cutaneous arteries are known to constrict in response to cooling via α2C-adrenoceptors. The involvement of α1-adrenoceptors in the cooling response has also recently been suggested by in vivo studies in mice. The present study was thus aimed to confirm it in the isolated mouse cutaneous plantar artery. Changes in vess...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: Goto K,Saito SY,Ishikawa T

    更新日期:2014-11-05 00:00:00

  • Inhibitors of Ca(2+)-dependent endopeptidases modulate morphine-induced effects in rats.

    abstract::The effects of inhibitors of Ca(2+)-dependent endopeptidases (antipain and leupeptin) on morphine analgesia, reinforcing properties of morphine and on the development of opiate physical dependence were studied. Male Wistar rats were used. The analgesic action of morphine in the tail-immersion test was increased signif...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: Lyupina YV,Sudakov SK,Yarygin VN

    更新日期:1996-05-23 00:00:00

  • Eugenol protects nicotine-induced superoxide mediated oxidative damage in murine peritoneal macrophages in vitro.

    abstract::The present work is aimed at evaluating the protective effect of eugenol against in vitro nicotine-induced toxicity in murine peritoneal macrophages, compared with N-acetylcysteine. Eugenol was isolated from Ocimum gratissimum and characterized by HPLC, FTIR, (1)H NMR. To establish most effective protective support, w...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: Kar Mahapatra S,Chakraborty SP,Majumdar S,Bag BG,Roy S

    更新日期:2009-11-25 00:00:00

  • The synergetic effect of edaravone and borneol in the rat model of ischemic stroke.

    abstract::Free radical production contributes to the early ischemic response and the neuroinflammatory response to injury initiates the second wave of cell death following ischemic stroke. Edaravone is a free radical scavenger, and borneol has shown anti-inflammatory effect. We investigated the synergistic effect of these two d...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: Wu HY,Tang Y,Gao LY,Sun WX,Hua Y,Yang SB,Zhang ZP,Liao GY,Zhou QG,Luo CX,Zhu DY

    更新日期:2014-10-05 00:00:00

  • Endomorphins 1 and 2 induce amnesia via selective modulation of dopamine receptors in mice.

    abstract::The involvement of dopamine receptors in the amnesic effects of the endogenous micro-opioid receptor agonists endomorphins 1 and 2 was investigated by observing step-down type passive avoidance learning in mice. Although the dopamine D1 receptor agonist R(+)-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine-7,8-diol hydroc...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: Ukai M,Lin HP

    更新日期:2002-06-20 00:00:00

  • Venlafaxine: acute and chronic effects on 5-hydroxytryptamine levels in rat brain in vivo.

    abstract::Venlafaxine is a dual serotonin (5-hydroxytryptamine, 5-HT) and noradrenaline uptake inhibitor which has been claimed to have an onset of antidepressant action which is faster than for other comparable drugs. The effects of venlafaxine on brain 5-HT levels in vivo have not yet been examined. Acute administration of ve...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: Gur E,Dremencov E,Lerer B,Newman ME

    更新日期:1999-05-07 00:00:00

  • Pentoxifylline inhibits angiogenesis via decreasing Dll4 and Notch1 expression in mouse proepicardial explant cultures.

    abstract::Pentoxifylline (PTX), a non-specific inhibitor of cAMP phosphodiesterases, is commonly used for treatment of peripheral vascular disorders although its direct action on endothelial cells is not well described. The aim of this study was to determine the influence of PTX on tubule formation and mRNA expression for angio...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: Niderla-Bielińska J,Bartkowiak K,Ciszek B,Czajkowski E,Jankowska-Steifer E,Krejner A,Ratajska A

    更新日期:2018-05-15 00:00:00

  • A therapeutic dose of zolpidem has limited abuse-like effects in drug-naïve females: a pilot study.

    abstract::Zolpidem has abuse potential, particularly among individuals with histories of drug abuse. This double-blind, placebo-controlled, cross over pilot study investigated the subjective effects of zolpidem (10 mg) in drug-naïve females. Over the course of a 5-h period vital signs were monitored and a series of computerized...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: Licata SC,Penetar DM,Dunlap S,Lukas SE

    更新日期:2008-11-19 00:00:00

  • LncRNA FAM83H-AS1 contributes to the radioresistance, proliferation, and metastasis in ovarian cancer through stabilizing HuR protein.

    abstract::Ovarian cancer (OC) is a major cause of cancer-related deaths in women all over the world. The easy metastasis of OC and the problem of radioresistance are serious issues remaining to be overcome. Thus, research on molecular mechanisms underlying is in urgent demand. Long non-coding RNAs (lncRNAs) are a class of RNAs ...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: Dou Q,Xu Y,Zhu Y,Hu Y,Yan Y,Yan H

    更新日期:2019-06-05 00:00:00

  • A-317491, a selective P2X3/P2X2/3 receptor antagonist, reverses inflammatory mechanical hyperalgesia through action at peripheral receptors in rats.

    abstract::The effect of A-317491 (5-([(3-Phenoxybenzyl)[(1S)-1,2,3,4-tetrahydro-1-naphthalenyl]amino]carbonyl)-1,2,4-benzenetricarboxylic acid), a recently described selective P2X3 and P2X(2/3) receptor antagonist, on inflammatory mechanical hyperalgesia was examined. In the rat Freund's complete adjuvant model of inflammatory ...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: Wu G,Whiteside GT,Lee G,Nolan S,Niosi M,Pearson MS,Ilyin VI

    更新日期:2004-11-03 00:00:00

  • Functional study on vasodilator effects of prostaglandin E2 in the newborn pig cerebral circulation.

    abstract::Cerebral vascular reactivity to prostaglandin E2 was investigated in newborn pigs using closed cranial windows. Exogenous prostaglandin E2 is a dilator of pial arterioles that elevates cyclic AMP in cortical cerebrospinal fluid. Pial arterioles are less sensitive to prostaglandin E2 than to the prostacyclin receptor a...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: Parfenova H,Leffler CW

    更新日期:1995-05-15 00:00:00

  • Vascular beta-adrenoceptor blocking activity of endotoxin and pertussis toxin from Bordetella pertussis in rats.

    abstract::Isolated and purified leucocytosis promoting factor (LPF), alternatively described as pertussis toxin, reduced the hypotension after beta 2-adrenoceptor stimulation with salbutamol as well as the negative chronotropic activity induced by the muscarinic receptor stimulant arecoline 4 days after its injection into rats....

    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: De Wildt DJ,De Jong Y,Nijkamp FP,Kreeftenberg JG

    更新日期:1986-08-15 00:00:00

  • Dopamine agonist-induced hyperglycemia in rats: structure-activity relationships and mechanisms of action.

    abstract::The concentration of blood glucose was measured in rats after administration of a number of drugs characterized as dopamine agonists. Compounds that cause release of dopamine, or agents that block the reuptake of dopamine, did not elevate blood glucose. Some direct dopamine receptor stimulants (lergotrile, bromocripti...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: Schmidt MJ,Root MA,Hall JL

    更新日期:1983-06-03 00:00:00

  • Synergy between retigabine and GABA in modulating the convulsant site of the GABAA receptor complex.

    abstract::The molecular mechanism underlying the activity of the novel antiepileptic drug retigabine is not yet fully understood. The aim of this study was to investigate whether retigabine interacts directly with the GABA(A) receptor complex (gamma-aminobutyric acid). Receptor-binding assays were conducted using rat brain memb...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: van Rijn CM,Willems-van Bree E

    更新日期:2003-03-19 00:00:00

  • Studies on beta-adrenoceptors mediating changes in mechanical events and adenosine 3',5'-monophosphate levels. Rat atria.

    abstract::Increasing concentrations of the functional antagonist carbachol resulted in a shift to the right of the dose-response curves for (--)-isoproterenol-induced positive chronotropic and inotropic responses and a reduction of the maximum degree of response that could be produced relative to that produced by theophylline. ...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: Buckner CK,Torphy T,Costa DJ

    更新日期:1978-02-01 00:00:00

  • Cytoprotective effect of melatonin against hypoxia/serum deprivation-induced cell death of bone marrow mesenchymal stem cells in vitro.

    abstract::Bone marrow mesenchymal stem cells (MSCs) have been shown great potential for cardiac regeneration. However the therapeutic efficiency has become a major obstacle due to the poor survival of transplanted MSCs in ischemic cardiac tissue. Previous studies reported that melatonin could protect many different types of cel...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: Wang F,Zhou H,Du Z,Chen X,Zhu F,Wang Z,Zhang Y,Lin L,Qian M,Zhang X,Li X,Hao A

    更新日期:2015-02-05 00:00:00

  • Release of gonadotropin-releasing hormone by veratrine in a hypothalamic-pituitary coincubation.

    abstract::The effects of veratrine and veratridine on the release of gonadotropin-releasing hormone (GnRH) and luteinizing hormone (LH) from incubations of pituitary alone, hypothalamus alone, and coincubations of hypothalamus and pituitary were examined. Veratrine produced only small increases in LH secretion from pituitaries ...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: Powers CA,Johnson DC

    更新日期:1980-08-29 00:00:00

  • The glial cell modulator and phosphodiesterase inhibitor, AV411 (ibudilast), attenuates prime- and stress-induced methamphetamine relapse.

    abstract::Stress and renewed contact with drug (a "slip") have been linked to persisting relapse of methamphetamine abuse. Human brain microglial activation has been linked with methamphetamine abuse, and inhibitors of glial cell activation, certain phosphodiesterase (PDE) inhibitors, and glial cell derived neurotrophic factor ...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: Beardsley PM,Shelton KL,Hendrick E,Johnson KW

    更新日期:2010-07-10 00:00:00

  • JTT-608 controls blood glucose by enhancement of glucose-stimulated insulin secretion in normal and diabetes mellitus rats.

    abstract::We investigated the pharmacological effects of a new anti-hyperglycemic agent, JTT-608 [trans-4-(4-methylcyclohexyl)-4-oxobutyric acid], in normal and neonatally streptozotocin-treated rats. In normal rats, JTT-608 improved glucose tolerance at 3-30 mg/kg, doses that did not cause a decrease in fasting blood glucose l...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: Ohta T,Furukawa N,Yonemori F,Wakitani K

    更新日期:1999-02-12 00:00:00

  • Prevention of aortic calcification by etidronate in the renal failure rat model.

    abstract::Our recent clinical study indicated that etidronate may inhibit the progression of aortic calcification in hemodialysis patients. To determine whether etidronate inhibits aortic calcification in renal failure rats, renal failure was induced by subtotal nephrectomy, in which 5/6 of the kidneys were removed. Significant...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: Tamura K,Suzuki Y,Matsushita M,Fujii H,Miyaura C,Aizawa S,Kogo H

    更新日期:2007-03-08 00:00:00

  • Inhibitory effect of sevoflurane on nitric oxide release from cultured endothelial cells.

    abstract::We investigated the effect of sevoflurane (fluoromethyl-2,2,2-trifluoro-1-(trifluoromethyl) ethylether) on intracellular calcium concentration ([Ca2+]i) and nitric oxide (NO) release from cultured porcine aortic endothelial cells using fura-2 fluorometry, and direct (ESR spectrometry with NO-trapping by 2-(4-carboxyph...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: Az-ma T,Fujii K,Yuge O

    更新日期:1995-03-15 00:00:00

  • Effects of cimetidine, atropine and pirenzepine on basal and stimulated gastric acid secretion in the rat.

    abstract::The gastric anti-secretagogue effects of cimetidine (a histamine H2-receptor antagonist) and of atropine (a non-selective muscarinic receptor antagonist) and pirenzepine (a selective muscarinic M1-receptor antagonist) were examined in conscious gastric fistula rats both under basal conditions and after stimulation wit...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: Ekelund M,Håkanson R,Vallgren S

    更新日期:1987-06-19 00:00:00

  • Gender difference in the role of endothelium-derived relaxing factors modulating renal vascular reactivity.

    abstract:UNLABELLED:This study analyzed the role of nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF) in gender differences in the renal vascular reactivity of rats. Renal responses to vasoconstrictors and vasodilators were studied in isolated kidneys from male and female rats under basal conditions, after...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: Wangensteen R,Moreno JM,Sainz J,Rodríguez-Gómez I,Chamorro V,Luna Jde D,Osuna A,Vargas F

    更新日期:2004-02-23 00:00:00

  • Effects of yohimbine on naloxone-induced antinociception in a rat model of inflammatory hyperalgesia.

    abstract::Effects of the alpha2-adrenoceptor antagonist yohimbine on the antinociception produced by a low dose of naloxone were examined in a rat model of carrageenan-induced inflammation. In rats receiving saline prior to naloxone injection, the low dose of naloxone (5 microg/kg, i.p.) significantly prolonged paw withdrawal l...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: Tsuruoka M,Hiruma Y,Matsutani K,Matsui Y

    更新日期:1998-05-08 00:00:00

  • Effect of Ca2+ entry blockers on myosin light-chain kinase and protein kinase C.

    abstract::Thirteen Ca2+ entry blockers were compared with respect to their inhibitory effects on the activity of smooth muscle myosin light-chain kinase and smooth muscle protein kinase C, and the Ca2+-induced contraction of basilar artery rings. Comparison of the IC50 values obtained for these compounds, suggests that with the...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: Schächtele C,Wagner B,Rudolph C

    更新日期:1989-04-12 00:00:00

  • Apomorphine-induced locomotor stimulation in developing rats treated with 6-hydroxydopa.

    abstract::Apomorphine-induced locomotor stimulation was investigated in the developing rat following injection with 6-hydroxydopa at birth. Treatment with 6-hydroxydopa potentiated locomotor responsiveness to apomorphine in the 20-day-old rat. The 6-hydroxydopa-treated animal at 30 days, however, was less sensitive to the drug ...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: Nomura Y,Segawa T

    更新日期:1978-07-15 00:00:00

  • Targeting DNA and mutant p53 by a naphthalimide derivative, NA20, exhibits selective inhibition in gastric tumorigenesis by blocking mutant p53-EGFR signaling pathway.

    abstract::Mutations of p53 in cancer cells not only subvert its antiproliferative properties but can also promote various oncogenic responses through a gain-of-function activity. Pharmacological manipulation of the mutant p53 pathway by specific compounds could be an effective strategy for cancer therapy. We show here that gain...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: Zhang G,Li L,Bi J,Wu Y,Li E

    更新日期:2020-11-15 00:00:00

  • The involvement of DAMPs-mediated inflammation in cyclophosphamide-induced liver injury and the protection of liquiritigenin and liquiritin.

    abstract::Cyclophosphamide (CPA) is a chemotherapeutic drug widely used in the treatment of breast cancer or leukemia in clinic. However, CPA was reported to have hepatotoxicity. This study aims to observe the engaged mechanism of CPA-induced liver injury in mice and the protection of liquiritin (LQ) and liquiritigenin (LG). Li...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: Chen M,Zhang C,Zhang J,Kai G,Lu B,Huang Z,Ji L

    更新日期:2019-08-05 00:00:00

  • Acute delta-opioid receptor activation induces CREB phosphorylation in NG108-15 cells.

    abstract::A growing body of evidence supports an important role of the transcription factor cAMP responsive element binding protein (CREB) in mediating opioid-induced changes in the cAMP pathway. Regulation of CREB and subsequent changes in gene expression may underlie some long-term cellular adaptations associated with the adm...

    journal_title:European journal of pharmacology

    pub_type: 杂志文章


    authors: Bilecki W,Höllt V,Przewłocki R

    更新日期:2000-02-25 00:00:00