Abstract：
:1. Primary porcine hepatocytes and enterocytes were isolated and cultured in Williams' E medium for up to 10 days to investigate potential organ differences in the metabolism of the immunosuppressive compound tacrolimus (FK 506) and of two investigational drugs (KC11346 and KC12291). Using LC-MS (FK506) and HPLC-FL (KC 11346/12291) a number of metabolites with identical mass and/or identical retention time could be detected. 2. In the case of tacrolimus hepatocytes and enterocytes produced the same spectrum of metabolites, e.g. bisdemethyl-tacrolimus, demethyl-tacrolimus, demethyl-hydroxy-tacrolimus and hydroxy-tacrolimus, albeit at varying intensities. 3. Treatment of enterocyte cultures with dexamethasone increased the overall metabolite formation very significantly (up to 36 fold). 4. The metabolism of tacrolimus was also studied with preparations of insect cells, that express specifically high levels of individual human cytochrome P450 (CYP) isoenzymes. All metabolites could be generated with microsomal preparations specifically expressing CYP3A4, but hydroxy-tacrolimus was exclusively produced by CYP3A5. 5. In the case of the investigational drugs KC 11346 and KC 12291 only three metabolites were formed by cultured enterocytes whereas hepatocytes produced 10 and 20 metabolites, respectively. 6. When assessed at the protein level CYP1A and CYP3A were expressed in cultures of porcine enterocytes for up to 10 days but porcine hepatocytes expressed additionally CYP2C9/10. 7. In conclusion, primary enterocytes and hepatocytes can be successfully cultured for several days while maintaining mono-oxygenase activity and may therefore be used as a tool for studying intestinal and hepatic metabolism.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Bader A,Hansen T,Kirchner G,Allmeling C,Haverich A,Borlak JTdoi
10.1038/sj.bjp.0703062subject
Has Abstractpub_date
2000-01-01 00:00:00pages
331-42issue
2eissn
0007-1188issn
1476-5381journal_volume
129pub_type
杂志文章abstract：:1. Using a guinea-pig model of allergic asthma, in which the animals display early (0-5 h) and late phase (8-23 h after antigen challenge) bronchoconstrictor reactions, the function of prejunctional inhibitory M2 and postjunctional M3 receptors in isolated tracheal preparations have been investigated. In addition, car...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1995.tb13286.x
更新日期：1995-02-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Memantine and ketamine are clinically used, open-channel blockers of NMDA receptors exhibiting remarkable pharmacodynamic similarities despite strikingly different clinical profiles. Although NMDA channel gating constitutes an important difference between memantine and ketamine, it is unclear how...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.13007
更新日期：2015-03-01 00:00:00
abstract：:1 Adenosine, adenosine monophosphate and adenosine triphosphate (ATP) depressed the firing rate of neurones in the rat cerebral cortex when applied by microinontophoresis. 2 4-Aminopyridine, also applied iontophoretically blocked the depressant effects of the purines, without affecting responses to gamma-aminobutyric ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1980.tb08720.x
更新日期：1980-11-01 00:00:00
abstract：:1. The effects of the lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA) on the ionic currents of rat carotid body type I cells were investigated by use of whole-cell and outside-out patch clamp techniques. 2. NDGA (5-50 microM) produced a concentration-dependent inhibition of whole-cell K+ currents at all activa...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0701452
更新日期：1997-11-01 00:00:00
abstract：:Although previous reports have suggested that the sigma 1 (sigma(1)) receptor may be involved in pain sensation, its specific site of action has not been elucidated. The aim of present study was to determine the role of the spinal sigma(1) receptor in formalin-induced pain behavior, spinal cord Fos expression and phos...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0706764
更新日期：2006-06-01 00:00:00
abstract：:ZK110841 and AH6809, an agonist and an antagonist of prostaglandin DP-receptors on human platelets, were evaluated with a fibroblastic cell line from bovine embryonic trachea (EBTr) which specifically responds to prostaglandin D2 (PGD2). ZK110841, equipotent to PGD2, elevated the adenosine 3':5'-cyclic monophosphate (...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1990.tb14645.x
更新日期：1990-01-01 00:00:00
abstract：:In anaesthetized dogs at room temperatures of 28-33 degrees C, the cerebral ventricles were perfused with artificial CSF from the left lateral ventricular to the aqueductal cannulae. The animals' temperatures were recorded from the rectum. Addition of Ca(++) in excess to the artificial CSF perfusing the ventricles pro...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1973.tb08547.x
更新日期：1973-12-01 00:00:00
abstract：:1. Intravenous administration of leukotriene C4 (LTC4) and LTD4 (1-10 nmol kg-1) caused a dose-dependent increase in secretion of glandular-kallikrein in the bronchial washings of guinea-pigs, as measured by cleavage of a synthetic substrate and the formation of kinin. LTC4 was more potent than LTD4 and pilocarpine wa...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1992.tb09031.x
更新日期：1992-03-01 00:00:00
abstract：:1. 8-Hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), gepirone, buspirone and ipsapirone dose-dependently antagonized the head-shakes induced by 1-(2,5-dimethoxy 4-iodophenyl)-2-amino propane hydrochloride (DOI) (1.0 mg kg-1) in mice, when these agents were given i.p. 10 min beforehand. 2. para-Chlorophenylalanine (...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1993.tb13727.x
更新日期：1993-08-01 00:00:00
abstract：:1. The potassium-sparing diuretic, amiloride, has been shown to inhibit the Na/Ca exchange system in various preparations. The effects of this drug have been investigated on the contractions of guinea-pig aortic strips elicited by reduction of external K, by addition of ouabain and by removal of external Na. 2. Amilor...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1988.tb10316.x
更新日期：1988-03-01 00:00:00
abstract：:The rat isolated right atrium (frequency response) and progesterone-treated rat uterus (relaxation) were used to examine the beta 1- and beta 2-adrenoceptor stimulatory effects of alprenolol, oxprenolol and pindolol. In addition, the beta 1-adrenoceptor stimulatory effect of practolol was studied in the right atrium. ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1986.tb14582.x
更新日期：1986-04-01 00:00:00
abstract：:1. The vascular actions of the proteinase-activated receptor-2-activating peptides (PAR2APs), SLIGRL-NH2 (SL-NH2) and SLIGKV-NH2 (KV-NH2) as well as the reverse-sequence peptide, LSIGRL-NH2 (LS-NH2) and an N-acylated PAR2AP derivative, trans-cinnamoyl-LIGRLO-NH2 (tcLI-NH2), were studied in rat intact and endothelium-d...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0701726
更新日期：1998-04-01 00:00:00
abstract：:1 The present study examined effects of agonist enzymes and receptor-activating peptides for protease-activated receptors (PARs) on duodenal motility in the rat, and also investigated possible mechanisms underlying the evoked responses. 2 Thrombin at 0.03-0.1 microM and the PAR-1-activating peptide SFLLR-NH2 at 3-100 ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0702755
更新日期：1999-10-01 00:00:00
abstract：:1. The central and regional cardiovascular responses to intravenous (0.3, 1.0, 3.0 and 10.0 micrograms kg-1 min-1) and intracoronary (0.3, 0.9, 3.0 and 4.5 micrograms kg-1 min-1) infusions of elgodipine, a phenyldihydropyridine, and its solvent were studied in anaesthetized pigs. 2. Elgodipine (i.v.) caused dose-depen...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1990.tb14708.x
更新日期：1990-02-01 00:00:00
abstract：:1. Milacemide is a glycine prodrug which is both an inhibitor and a substrate for monoamine oxidase-type B (MAO-B) and also an inhibitor of MAO-type A (MAO-A). Its effects on dopamine and 5-hydroxytryptamine (5-HT) metabolism in rat frontal cortex tissue and dialysate were evaluated. 2. Dialysate dopamine concentratio...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1992.tb14210.x
更新日期：1992-01-01 00:00:00
abstract：:5-Hydroxytryptamine (5-HT, 5-160 microgram kg-1) injected intravenously in pentobarbitone-anaesthetized, open-chest cats caused dose-dependent increases in pulmonary arterial and intratracheal pressures. There was also a marked systemic hypotension and bradycardia. The pulmonary effects were completely prevented by ke...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1983.tb10033.x
更新日期：1983-10-01 00:00:00
abstract：:1 Anthopleurin-B (AP-B, greater than 3 x 10(-9) M), a newly isolated polypeptide from sea anemone (Anthopleura xanthogrammica), caused powerful rhythmic contractions in the guinea-pig isolated vas deferens. The other polypeptides anthopleurin-A from A. xanthogrammica and anthopleurin-C from A. elegantissima, elicited ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1981.tb09951.x
更新日期：1981-09-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Tolerance induced by morphine and other opiates remains a major unresolved problem in the clinical management of pain. There is now good evidence for the importance of MAPKs in morphine-induced antinociceptive tolerance. A member of the MAPK kinase kinase family, TGF-β activated kinase 1 (TAK1) i...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.13094
更新日期：2015-06-01 00:00:00
abstract：:1. Conscious normotensive cynomolgus monkeys were chronically instrumented for the measurement of arterial blood pressure and heart rate to investigate the relationships between the plasma concentration, suppression of the pressor response to angiotensin II (AII), compensatory increase in plasma AII, and hypotensive e...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1994.tb14036.x
更新日期：1994-01-01 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：:Some 865 genes in man encode G-protein-coupled receptors (GPCRs). The heterotrimeric guanine nucleotide-binding proteins (G-proteins) function to transduce signals from this vast panoply of receptors to effector systems including ion channels and enzymes that alter the rate of production, release or degradation of int...
journal_title：British journal of pharmacology
pub_type： 历史文章,杂志文章,评审
doi：10.1038/sj.bjp.0706405
更新日期：2006-01-01 00:00:00
abstract：:1 Prolonged exposure (6-12 h) of rat aorta to alpha1-adrenergic receptor (alpha(1)AR) agonist phenylephrine (Phe) leads to a decrease in alpha(1)AR-mediated vasoconstriction. This reduced responsiveness to alpha(1)AR stimulation was strongly dependent on the intactness of the endothelium. 2 We examined the effect of P...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0706177
更新日期：2005-05-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Inhalation of the superantigen,staphylococcal enterotoxin B (SEB), leads to the activation of the host T and invariant natural killer (iNK) T cells, thereby resulting in acute lung inflammation and respiratory failure but the underlying mechanism(s) of disease remain elusive, with limited treatme...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.2012.02063.x
更新日期：2012-11-01 00:00:00
abstract：:In this issue, BJP is proud to publish an Endothelium Themed Section to celebrate the life of Robert F. Furchgott, who died on May 19th 2009. It is 30 years since he discovered endothelium-derived relaxant factor and a decade since he was awarded the Nobel Prize for this work. His discovery has led to an array of new ...
journal_title：British journal of pharmacology
pub_type： 社论
doi：10.1111/j.1476-5381.2009.00366.x
更新日期：2009-06-01 00:00:00
abstract：:1. Chronic administration of the benzodiazepine inverse agonist FG 7142 has previously been shown to induce seizure activity in mice. In the present study we have investigated the effects of acute and chronic treatment with FG 7142 in mice on the levels of acetylcholinesterase activity in cortex, hippocampus, midbrain...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1990.tb14127.x
更新日期：1990-11-01 00:00:00
abstract：:1 Prostaglandin and thromboxane release from the term pregnant (Day 22) rat uterus in vitro has been measured by radioimmunoassay and gas chromatography combined with mass spectrometry. 2 Prostacyclin (prostaglandin I2, PGI2) and thromboxane A2 (TXA2) (measured as their metabolites, 6-oxo-PGF1 alpha and TXB2, respecti...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1981.tb16773.x
更新日期：1981-05-01 00:00:00
abstract：:Obesity is a common metabolic disorder that has become a widespread epidemic in several countries. Sex and gender disparities in the prevalence of cardiovascular disease (CVD) have been well documented with premenopausal women having a lower incidence of CVD than age-matched men. However, women are more likely than me...
journal_title：British journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1111/bph.14783
更新日期：2019-11-01 00:00:00
abstract：:1. In order to determine whether the renin-angiotensin system is involved in myocardial ischaemia-reperfusion injury, we investigated and compared the effects on infarct size of two different drugs which interfere with this system, i.e., an angiotensin II (AT1) antagonist, EXP3174, and an angiotensin I-converting enzy...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1993.tb13908.x
更新日期：1993-11-01 00:00:00
abstract：:1. The irreversible opioid receptor antagonist beta-chlornaltrexamine (beta-CNA) has been shown previously to have agonist activity in the guinea-pig ileum preparation. However, the receptor type or types mediating this effect have not been established. 2. In this study, the agonism of beta-CNA was investigated by use...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1988.tb16569.x
更新日期：1988-09-01 00:00:00
abstract：:1. The release of prostaglandin D2 (PGD2) during immediate allergic reactions in human skin was investigated in vivo and in vitro. 2. Skin exudates were collected from abraded sites on the thigh of atopic subjects sensitive to D. pteronyssinus antigen and from non-atopic control subjects. Challenge with antigen caused...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1988.tb11588.x
更新日期：1988-07-01 00:00:00
