Abstract：
:We investigated the effects of branched-chain amino acids on DNA synthesis and proliferation in primary cultures of adult rat hepatocytes. Of the branched-chain amino acids, only leucine (10(-5)-10(-3) M) induced hepatocyte DNA synthesis and proliferation in a time- and dose-dependent manner. The addition of valine or isoleucine on its own had no significant effects on the hepatocyte DNA synthesis and proliferation. When combined, isoleucine competitively antagonized leucine-stimulated hepatocyte mitogenesis. U73122 (10(-6) M), AG1478 (10(-7) M), wortmannin (10(-7) M), PD98059 (10(-6) M) and rapamycin (10 ng/ml) inhibited the ability of leucine to stimulate the hepatocyte DNA synthesis and proliferation, suggesting that phospholipase C, tyrosine kinase, phosphatidylinositol 3-kinase, mitogen-activated protein (MAP) kinase, and p70 S6 kinase are involved in leucine signaling. The mitogenic effects of leucine are completely abolished by the addition of anti-transforming growth factor-alpha (TGF-alpha) antibody to the culture medium. Furthermore, leucine stimulated TGF-alpha secretion into the culture medium and the leucine effect was inhibited by U73122. Isoleucine alone had no significant effect on TGF-alpha secretion but this agent blocked leucine-induced TGF-alpha secretion. The results suggest that leucine triggers TGF-alpha secretion through a putative leucine receptor. The secreted TGF-alpha then stimulates hepatocyte DNA synthesis and proliferation through activation of TGF-alpha receptor to induce tyrosine kinase/MAP kinase activity and other downstream growth-related signal transducers.
journal_name
Eur J Pharmacoljournal_title
European journal of pharmacologyauthors
Kimura M,Ogihara Mdoi
10.1016/j.ejphar.2005.01.011keywords:
subject
Has Abstractpub_date
2005-03-14 00:00:00pages
167-80issue
3eissn
0014-2999issn
1879-0712pii
S0014-2999(05)00012-9journal_volume
510pub_type
杂志文章abstract：:To evaluate the cardiac effect of an inhibitor of angiotensin-converting enzyme, the effect of intracoronary (i.c.) captopril on coronary blood flow and regional myocardial function was examined in the anesthetized open-chest dog. Blood flow of the left circumflex coronary artery (LCX), left ventricular pressure (LVP)...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(85)90023-8
更新日期：1985-03-26 00:00:00
abstract：:Animal studies have shown that endogenous estrogens such as 17β-estradiol (E2) can modulate lipid profiles in vivo, and this effect is generally thought to be mediated by the estrogen receptors (ERs). The present study sought to test a hypothesis that some of the endogenous estrogen metabolites that have very weak est...
journal_title：European journal of pharmacology
pub_type： 杂志文章
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更新日期：2017-04-05 00:00:00
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(80)90141-7
更新日期：1980-08-29 00:00:00
abstract：:Cocaine and several sigma receptor ligands inhibit dopamine uptake via a common site. This is evidenced by a concentration-dependent inhibition of dopamine uptake and displacement of the binding of [3H]WIN 35,428 (also called CFT), a cocaine analog with high affinity for the dopamine transporter. Since several sigma r...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(93)90381-q
更新日期：1993-10-19 00:00:00
abstract：:We studied the effects of inhaled formoterol (0.75 mg/ml, 60 breaths = 26 micrograms), a long-acting beta 2-adrenoceptor agonist, or of the more short-acting drug, salbutamol (25 mg/ml, 60 breaths = 875 micrograms), on acute airflow obstruction and airway microvascular leakage (MVL) induced by inhaled histamine in ane...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(91)90197-x
更新日期：1991-01-25 00:00:00
abstract：:A mixture of dexamphetamine and chlordiazepoxide induces hyperactivity in both mice and rats. This type of hyperactivity has been proposed as an animal model of mania. Magnesium valproate itself had little influence on the activity of normal mice and rats. Acute pretreatment of mice with magnesium valproate (75-300 mg...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(93)90266-k
更新日期：1993-06-24 00:00:00
abstract：:The effects of clonidine and dl-propranolol on negative pressure breathing-induced diuresis in chloralose-anaesthetized dog were studied. Clonidine (10 microgram/kg i.v.) suppressed the diuretic response, whereas dl-propranolol (1 mg/kg i.v.) was inactive. ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(81)90579-3
更新日期：1981-07-10 00:00:00
abstract：:Cocaine is eliminated and detoxified principally through the metabolism of nonspecific plasma and tissue esterases. Microsomal oxidative metabolism is of importance in cocaine N-demethylation, this being a principal pathway of cocaine bioactivation and hepatotoxicity. The contribution of different cytochrome P450 (CYP...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0926-6917(94)90078-7
更新日期：1994-01-03 00:00:00
abstract：:Ifoxetine (CGP 15210 G; (+/-)-bis-[cis-3-hydroxy-4-(2,3-dimethyl-phenoxy)]-piperidine sulfate) prevented the depletion of serotonin (5-HT) induced by H 75/12 and p-chloromethamphetamine in the rat brain, and that caused by endogenously released dopamine after the combined administration of haloperidol and amfonelic ac...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(86)90177-9
更新日期：1986-10-14 00:00:00
abstract：:Oxymetazoline was recognized with nanomolar affinity by 5-HT1A, 5-HT1B and 5-HT1D binding sites and mimicked the effects of 5-hydroxytryptamine with about the same potency and intrinsic activity as the endogenous amine in the corresponding functional tests. At 5-HT1C receptors, oxymetazoline behaved as a mixed agonist...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(91)90432-p
更新日期：1991-04-17 00:00:00
abstract：:We have characterized the rat prostanoid EP1, EP2, EP3alpha and EP4 receptor subtypes cloned from spleen, hepatocyte and/or kidney cDNA libraries. Comparison of the deduced amino acid sequences of the rat EP receptors with their respective homologues from mouse and human showed 91% to 98% and 82% to 89% identity, resp...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(97)01383-6
更新日期：1997-12-11 00:00:00
abstract：:In this study, we investigated whether spinal noradrenergic and serotonergic systems are involved in the antinociception induced by the novel pyrazolines 3-methyl- and 3-phenyl-5-hydroxy-5-trichloromethyl-4,5-dihydro-1H-1-pyrazole-1-carboxyamide (MPCA and PPCA, respectively), and the pyrazolinone dipyrone in the aceti...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2004.05.045
更新日期：2004-08-02 00:00:00
abstract：:Effects of ouabain on force of contraction were compared in electrically driven isolated tissue preparations of guinea-pig left atria and diaphragm. A distinct and steady positive inotropic effect of ouabain was observed in atrial preparations, whereas in diaphragm preparations, ouabain produced only a slight and tran...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(81)90188-6
更新日期：1981-05-22 00:00:00
abstract：:We investigated the acute and chronic effects of alpha 2-adrenoceptor and muscarinic receptor agonists on dihydropyridine-sensitive voltage-dependent Ca2+ channels in spinal cord-dorsal root ganglion cocultures. Clonidine and oxotremorine inhibited the voltage-dependent Ca2+ influx (42 +/- 2% and 35 +/- 6% with 100 mi...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0922-4106(93)90060-m
更新日期：1993-01-04 00:00:00
abstract：:Gender-related differences in susceptibility to stress and stress-related disorders such as depression, and in response to treatment with antidepressants have been observed, but the underlying molecular mechanisms are still unknown. Considering the role of glucocorticoid hormones in the systemic reaction against stres...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2009.02.038
更新日期：2009-04-17 00:00:00
abstract：:The tripeptides SD-34 and SD-25 induced atropine-, guanethidine-, antihistaminics-resistant but naloxone-sensitive contractions of isolated rat distal colon. They appeared to act on an opioid receptor, probably of the mu subtype, distinct from those for methionine enkephalin and morphine, because the pA2 values of nal...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(84)90312-1
更新日期：1984-04-13 00:00:00
abstract：:The effects of omega-conotoxin GVIA (omega-CgTx), a peptide isolated from the venom of a marine mollusc, were studied in rat hippocampal neurons. Intracellular recordings from the CA1 area were made for the purpose in in vitro slice preparations. Omega-CgTx (0.1-1 microM) rapidly and irreversibly blocked the EPSP and ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(89)90318-x
更新日期：1989-12-19 00:00:00
abstract：:The functional role of metabotropic glutamate (mGlu) receptors in the rat dentate gyrus was investigated. By using extracellular recording techniques in slices, it was found that the depression induced by the mGlu receptor agonist (1S,3R)-1-amino-cyclopentane-1,3-dicarboxylate (ACPD) was mediated through the mGlu grou...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(95)00560-9
更新日期：1995-12-29 00:00:00
abstract：:The effect of monocrotaline-induced pulmonary hypertension on alpha(1)-adrenoceptor-mediated contractions of pulmonary artery segments was studied. In control and monocrotaline-treated rats, noradrenaline evoked concentration-dependent contractions of the pulmonary artery. There was no change in the potency and affini...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2003.10.001
更新日期：2003-12-15 00:00:00
abstract：:The effects of the unilateral application of d-amphetamine, benztropine, haloperidol and thioproperazine to one substantia nigra on the release of 3H-dopamine (3H-DA) in the two caudate nuclei were examined in halothane-anesthetized cats. For this purpose animals were implanted with push-pull cannulae and 3H-DA was es...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(79)90135-3
更新日期：1979-01-15 00:00:00
abstract：:Acute lung injury (ALI) is a common severe clinical syndrome in intensive care unit. Inflammation has been reported to play a critical role in the development of ALI. Cordycepin, an active component isolated from Cordyceps militaris, has been reported to have anti-inflammatory effects. However, the anti-inflammatory e...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2017.10.029
更新日期：2018-01-05 00:00:00
abstract：:meta-Substituted 2-chlorophenyl(imino)imidazolidines of the clonidine-type (2,3- and 2,5-substituted derivatives) were used in attempts to discriminate between alpha-adrenergic effects (central hypotensive and peripheral hypertensive activities) in rats. The central hypotensive activity of four pairs of substitution i...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(81)90185-0
更新日期：1981-05-22 00:00:00
abstract：:The presence of neuronal nicotinic acetylcholine receptors in rabbit corpus cavernosum tissue and possible mechanisms underlying the potentiation of electrical field stimulation induced relaxation by nicotine were analyzed. In corpus cavernosum tissue strips nicotine (3 x 10(-5) M) and acetylcholine (10(-3) M) produce...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2006.11.053
更新日期：2007-03-08 00:00:00
abstract：:DSP-4 (N-(2-chloroethyl)-ethyl-2-bromobenzylamine) a novel neurotoxin which destroys central noradrenaline neurones after peripheral injection was administered to rats (50 mg/kg X 2). This procedure did not alter activity responses to quipazine (7.5 mg/kg) or apomorphine (0.2 mg/kg) but prevented their enhancement by ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(85)90593-x
更新日期：1985-09-10 00:00:00
abstract：:In addition to its well-known interaction with ionotropic and metabotropic receptors, glutamate may, at high concentrations, interfere with a cystine-glutamate antiport designated as Xc- and lead to a significant decrease in cystine uptake and intracellular glutathione level. These effects, in turn, may induce death i...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(97)00155-6
更新日期：1997-05-12 00:00:00
abstract：:By far the most attention has been paid to the deleterious actions of nonsteroidal anti-inflammatory drugs (NSAIDs), including isoform selective agents that inhibit cyclooxygenase (COX), on the upper gastrointestinal tract, particularly the gastric and duodenal mucosa. However, recent studies confirm a relatively high...
journal_title：European journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.ejphar.2004.07.042
更新日期：2004-10-01 00:00:00
abstract：:We investigated the endothelin production and endothelin receptor activity of pericardial mesothelial cells obtained from spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats. The pericardial mesothelial cells were maintained in vitro and the production of endothelin-1 by these cells was evaluated by usin...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(98)00110-1
更新日期：1998-04-24 00:00:00
abstract：:beta-Carbolines (including harmane and pinoline) stimulate insulin secretion by a mechanism that may involve interaction with imidazoline I(3)-receptors but which also appears to be mediated by actions that are additional to imidazoline receptor agonism. Using the MIN6 beta-cell line, we now show that both the imidazo...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2004.08.018
更新日期：2004-10-06 00:00:00
abstract：:Exposure to cold (4 degrees C) of catheterized rats acclimated to 20 degrees C resulted in a progressive increase in plasma noradrenaline (NA) concentrations which reached values consistently more than twice the basal ones (20 degrees C) by about 30 min. No further increase in plasma NA levels were detected when the c...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(81)90478-7
更新日期：1981-01-29 00:00:00
abstract：:A single dose of 50 mg chlorimipramine was followed by a rapid and pronounced decrease in [3H]imipramine binding to platelet membranes. Incubation of human platelets or platelet membranes with 25 nM chlorimipramine similarly reduced [3H]imipramine binding. Imipramine, desmethylchlorimipramine, chlorpromazine and some ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(86)90753-3
更新日期：1986-07-15 00:00:00
