Abstract：
BACKGROUND AND PURPOSE:Carboxylesterases (CEs) metabolize a wide range of xenobiotic substrates including heroin, cocaine, meperidine and the anticancer agent CPT-11. In this study, we have purified to homogeneity human liver and intestinal CEs and compared their ability with hydrolyse heroin, cocaine and CPT-11. EXPERIMENTAL APPROACH:The hydrolysis of heroin and cocaine by recombinant human CEs was evaluated and the kinetic parameters determined. In addition, microsomal samples prepared from these tissues were subjected to chromatographic separation, and substrate hydrolysis and amounts of different CEs were determined. KEY RESULTS:In contrast to previous reports, cocaine was not hydrolysed by the human liver CE, hCE1 (CES1), either as highly active recombinant protein or as CEs isolated from human liver or intestinal extracts. These results correlated well with computer-assisted molecular modelling studies that suggested that hydrolysis of cocaine by hCE1 (CES1), would be unlikely to occur. However, cocaine, heroin and CPT-11 were all substrates for the intestinal CE, hiCE (CES2), as determined using both the recombinant protein and the tissue fractions. Again, these data were in agreement with the modelling results. CONCLUSIONS AND IMPLICATIONS:These results indicate that the human liver CE is unlikely to play a role in the metabolism of cocaine and that hydrolysis of this substrate by this class of enzymes is via the human intestinal protein hiCE (CES2). In addition, because no enzyme inhibition is observed at high cocaine concentrations, potentially this route of hydrolysis is important in individuals who overdose on this agent.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Hatfield MJ,Tsurkan L,Hyatt JL,Yu X,Edwards CC,Hicks LD,Wadkins RM,Potter PMdoi
10.1111/j.1476-5381.2010.00700.xsubject
Has Abstractpub_date
2010-08-01 00:00:00pages
1916-28issue
8eissn
0007-1188issn
1476-5381pii
BPH700journal_volume
160pub_type
杂志文章abstract：:Muscularis mucosa of the distal oesophagus of the opossum contains nerves which release acetylcholine and substance P(SP)-like material on field stimulation. The release of SP-like material appeared to be inhibited by the presence of exogenous muscarinic agonists and potentiated by muscarinic antagonists. Analysis of ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1986.tb10254.x
更新日期：1986-07-01 00:00:00
abstract：:1. We have investigated the influence of endothelial damage on the cerebrovascular reactivity to 5-hydroxytryptamine (5-HT) and some selective 5-HT agonists in canine basilar artery. 2. 5-HT, alpha-methyl 5-HT, GR 43175 (3-[2-dimethyl amino] ethyl-N-methyl-1H-indole-5-methane sulphonamide) and 5-carboxamidotryptamine ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1989.tb11797.x
更新日期：1989-01-01 00:00:00
abstract：:Mast cells participate in allergies, and also in immunity and inflammation by secreting proinflammatory cytokines. Flavonoids are naturally occurring polyphenolic plant compounds, one group of which -- the flavonols, inhibits histamine and some cytokine release from rodent basophils and mast cells. However, the effect...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0706246
更新日期：2005-08-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Parabens are commonly added in pharmaceutical, cosmetic and food products because of their wide antibacterial properties, low toxicity, inertness and chemical stability, although the molecular mechanism of their antibacterial effect is not fully understood. Some agonists of the transient receptor...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0707219
更新日期：2007-05-01 00:00:00
abstract：:1. The purpose of the present study was to determine the myocardial cytoprotective efficacy of azapropazone (AZA) and its potential site of action on neutrophil infiltration into reperfused/ischaemic myocardium with or without in vivo activation of neutrophils in rabbits. 2. AZA, 100 mg kg-1, was administered i.v. 10 ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1990.tb15813.x
更新日期：1990-06-01 00:00:00
abstract：:1. Insulin antibodies were induced in young guinea-pigs of both sexes weighing 300-400 g and housed in a room maintained at 28 degrees C+/-2 degrees C, by subcutaneous injection of 2 ml of freshly prepared insulin antigen emulsion between the shoulders once every month.2. To estimate the titre of serum antibody the se...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1971.tb07087.x
更新日期：1971-05-01 00:00:00
abstract：:(1) Here, we introduce a beta-casomorphin-5-derived cyclic pentapeptide, cCD-2 (Tyr-cyclo[d-Orn-Tyr(Bzl)-Pro-Gly]), which inhibits the cell growth of a variety of human cancer cell lines. (2) This opioid-derived peptide possesses only low affinity for mu-receptors, but enhances the agonist binding to mu-receptors in v...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0705416
更新日期：2003-09-01 00:00:00
abstract：:1. The effects of forskolin, a direct activator of adenylate cyclase and sodium nitroprusside, a direct activator of guanylate cyclase, were studied on rabbit isolated ear arteries preconstricted with 80 mM potassium. 2. Bolus injection of these two compounds resulted in vasodilatation. They had similar potencies in t...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1989.tb11873.x
更新日期：1989-03-01 00:00:00
abstract：:1 The activity and pulmonary metabolism of two peptides, 7-homo Pro-bradykinin and 8-homo Phe-bradykinin were studied in isolated systems. 2 Both analogues were about 50-70 times less active than bradykinin on the guinea-pig ileum and 70-160 times less active on isolated strips of cat terminal ileum. 3 The action of b...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1977.tb06985.x
更新日期：1977-01-01 00:00:00
abstract：:Recent advances have improved our understanding of the renin-angiotensin system (RAS). These have included the recognition that angiotensin (Ang)-(1-7) is a biologically active product of the RAS cascade. The identification of the ACE homologue ACE2, which forms Ang-(1-7) from Ang II, and the GPCR Mas as an Ang-(1-7) ...
journal_title：British journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1111/bph.12159
更新日期：2013-06-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Betulinic acid (BA) is a naturally occurring triterpenoid widely distributed throughout the plant kingdom. We previously reported that BA inhibits lipopolysaccharide (LPS)-induced interleukin-6 production through modulation of nuclear factor κB (NF-κB) in human peripheral blood mononuclear cells ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.2010.01112.x
更新日期：2011-03-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Memantine and marijuana smoking have been found to inhibit tremor in parkinsonian patients, although the observed effects were relatively weak. The tremorolytic effects of combinations of memantine and cannabinoids have not been studied. Here, we have evaluated the anti-tremor activity of memanti...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.14914
更新日期：2020-04-01 00:00:00
abstract：:1. The effects of some rapidly metabolized sympathomimetic amines, such as beta-phenylethylamine and p-tyramine, in eliciting hypertensive responses to reserpine in the anaesthetized rat, have been studied.2. Retardation of metabolism, by pretreatment with the monoamineoxidase inhibitors iproniazid or phenelzine, caus...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1972.tb07256.x
更新日期：1972-02-01 00:00:00
abstract：:1. The present study has compared the relative anti-aggregatory effect of various compounds which interfere with thromboxane (Tx) A2-dependent aggregation of human platelets in whole blood in vitro. These included the cyclo-oxygenase inhibitor aspirin, the TxA2 synthase inhibitor dazoxiben, the TxA2 (TP-) receptor blo...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1991.tb12200.x
更新日期：1991-02-01 00:00:00
abstract：:1. The effects of nipradilol, a beta-adrenoceptor antagonist which possesses a nitroxy group, on cytosolic Ca2+ concentration ([Ca2+]i), and on tension development were simultaneously measured by front-surface fluorometry and fura-2-loaded strips in the proximal portion of pig coronary arteries. 2. Nipradilol reduced ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1996.tb15343.x
更新日期：1996-04-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Allosteric modulators of ionotropic receptors and GPCRs might constitute valuable therapeutic tools for intervention in several diseases, including Parkinson's disease (PD). However, the possibility that some of these compounds could alter neurotransmission in health and disease has not been thor...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.12758
更新日期：2014-08-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Dilatation of cerebral and dural arteries causes a throbbing, migraine-like pain, indicating that these structures are involved in migraine. Clinical trials suggest that adenosine 5'-triphosphate-sensitive K(+) (K(ATP)) channel opening may cause migraine by dilatating intracranial arteries, inclu...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/bjp.2008.86
更新日期：2008-05-01 00:00:00
abstract：:1. The effects of several agonists of the metabotropic glutamate receptor (mGluR) were studied in adult rat striatal slices by measuring (i) KCl (30 mM)-induced output of previously taken up D-[3H]-aspartate (Asp), (ii) forskolin (30 microM)-induced adenosine 3':5'-cyclic monophosphate (cyclic AMP) accumulation and (i...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1993.tb13977.x
更新日期：1993-12-01 00:00:00
abstract：:1. Microvascular permeability in the mesentery and consequent leakage of protein into the peritoneum of spontaneously hypertensive rats (SHR) and normotensive rats (NTR) was measured in vivo by the extravasation of Evans blue dye. 2. In sensitized NTR, challenge with antigen produced extensive increases in dye extrava...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0701875
更新日期：1998-06-01 00:00:00
abstract：:1. We studied the effect of bradykinin on plasma exudation in the airways of the anaesthetized guinea-pig in vivo. Tissue content of extravasated Evans blue dye was used as an index of protein exudation in the larynx, trachea, main bronchi and intrapulmonary airways (i.p.a.). 2. Bradykinin increased the content of Eva...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1990.tb14150.x
更新日期：1990-11-01 00:00:00
abstract：:1.--The small protein Bv8, isolated from the amphibian skin, belongs to a novel family of secreted proteins linked to several biological effects. We describe the expression of Bv8/prokineticins and their receptors in mouse macrophages, and characterize their proinflammatory activities. 2.--The rodent analogue of Bv8, ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0706467
更新日期：2006-01-01 00:00:00
abstract：:1. Comparison of the rank order of potency of the natural prostanoids prostaglandin E2 (PGE2), PGD2, PGF2 alpha and carbaprostacyclin in stimulating cyclic AMP in Jurkat cells is consistent with the presence of an EP receptor. 2. Lack of responsiveness to the EP1/EP3 selective agonist, sulprostone, and the EP2 agonist...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1995.tb15030.x
更新日期：1995-08-01 00:00:00
abstract：:We examined whether a specific aminopeptidase P (APP) inhibitor, apstatin, increases vasodepressor responses to bradykinin in anaesthetized rats, and whether it would augment blood pressure responses further after treatment with the angiotensin-converting enzyme inhibitor (ACEi), lisinopril. Apstatin doubled the maxim...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1995.tb14897.x
更新日期：1995-01-01 00:00:00
abstract：BACKGROUND AND PURPOSE:It has been extensively reported that the leading anti-diabetic drug, metformin, exerts significant anticancer effects. This hydrophilic, cationic drug requires cation transporters for cellular entry where it activates its intracellular target, the AMPK signalling pathway. However, clinical resul...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.14694
更新日期：2019-08-01 00:00:00
abstract：:1. The aim of the present study was to test the effects of DAU 6215 (endo-N-(8-methyl-8-azabicyclo-[3.2.1]-octo-3-yl)-2,3-dihydro-2-ox o-1H- benzimidazole-1-carboxamide carboxamide hydrochloride), a newly synthesized, selective 5-hydroxytryptamine3 (5-HT3) antagonist, on the cell membrane properties and on characteriz...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1994.tb13132.x
更新日期：1994-06-01 00:00:00
abstract：:1. In some asthmatics, muscarinic receptor antagonists are effective in limiting bronchoconstrictor response, suggesting an abnormal cholinergic drive in these subjects. There is a growing body of evidences indicating that cholinergic neurotransmission is also enhanced by endothelin-1 (ET-1) in rabbit bronchi, mouse t...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0704395
更新日期：2001-12-01 00:00:00
abstract：:1. The purpose of this investigation was to examine the outputs of peptide histidine isoleucine (PHI) and vasoactive intestinal peptide (VIP) from the gastric corpus in response to stimulation of the peripheral (PVS) and central (CVS) ends of the vagus nerve and to compare the effects of PHI on gastric motility and bl...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1990.tb15787.x
更新日期：1990-06-01 00:00:00
abstract：BACKGROUND AND PURPOSE:The sodium channel is a primary target for treating central nervous system disorders such as epilepsy. In this study the anticonvulsant effect of BmK IT2, a sodium channel-specific neurotoxin, was evaluated in different animal models of epilepsy. EXPERIMENTAL APPROACH:Experiments were performed ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/bjp.2008.156
更新日期：2008-07-01 00:00:00
abstract：:1. To obtain direct evidence of abnormal eicosanoid biosynthesis in rats injected with anti-glomerular-basement-membrane antibodies (a-GBM), products derived from thromboxane A2 (TXA2) and prostacyclin (PGI2) were measured in 24 h urine collections before and after a-GBM. 2. Administration of a-GBM (9.5 mg) caused alb...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1991.tb09844.x
更新日期：1991-07-01 00:00:00
abstract：:1. Electrical stimulation of the mid-brain raphé in anaesthetized adrenalectomized rats produced a significant decrease in the forebrain content of 5-hydroxytryptamine (5-HT) and an increase in the concentration of 5-hydroxyindol-3-ylacetic acid (5-HIAA).2. Stimulation of peripheral sensory nerves did not influence ei...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1970.tb09550.x
更新日期：1970-05-01 00:00:00
