Abstract：
BACKGROUND AND PURPOSE:Next to its broad antimicrobial spectrum, the therapeutic advantages of the fluoroquinolone antimicrobial drug Danofloxacin-Mesylate (DM) are attributed to its rapid distribution to the major target tissues such as lungs, intestines and the mammary gland in animals. Previous analyses revealed that effective drug concentrations are achieved also in luminal compartments of these organs, suggesting that active transport proteins facilitate excretion into the luminal space. Members of the ATP-Binding Cassette (ABC) superfamily, including P-gp, BCRP and MRP2 are known to be expressed in many tissue barriers and in cell-membranes facing luminal compartments. Hence we hypothesized that DM is a substrate for one of these efflux-transporters. EXPERIMENTAL APPROACH:Confluent monolayers of Caco-2 cells, grown on microporous membranes in two-chamber devices were used. DM concentrations were measured by fluorimetric assay after HPLC of the culture media. KEY RESULTS:DM transport across Caco-2 cells was asymmetric, with a rate of secretion exceeding that of absorption. The P-gp inhibitors PSC833 and GF120918 and the MRP-inhibitor MK571 partially decreased the secretion of DM and increased its absorption rate. The BCRP inhibitor, Ko143, decreased secretion only at a concentration of 1 microM. When DM was applied together with ciprofloxacin, secretion as well as absorption of DM decreased. CONCLUSIONS AND IMPLICATIONS:DM is a substrate for the efflux transporters P-gp and MRP2, whereas the specific role of BCRP in DM transport needs further evaluation. These findings provide a mechanistic basis for the understanding of the pharmacokinetics of DM in healthy and diseased individuals.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Schrickx JA,Fink-Gremmels Jdoi
10.1038/sj.bjp.0706974subject
Has Abstractpub_date
2007-02-01 00:00:00pages
463-9issue
4eissn
0007-1188issn
1476-5381pii
0706974journal_volume
150pub_type
杂志文章abstract：:1. The diversity of alpha(2) and purinergic autoreceptor actions on action potential evoked calcium transients in single varicosities has been investigated using the calcium indicator Oregon Green 488 BAPTA-1. 2. During long trains of impulses (10 Hz for 30 s), the change in calcium concentration in varicosities from ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0702984
更新日期：1999-12-01 00:00:00
abstract：:(1) Stimulation of the vanilloid receptor-1 (TRPV1) results in the activation of nociceptive and neurogenic inflammatory responses. Poor specificity and potency of TRPV1 antagonists has, however, limited the clarification of the physiological role of TRPV1. (2) Recently, iodo-resiniferatoxin (I-RTX) has been reported ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0705110
更新日期：2003-03-01 00:00:00
abstract：:Adrenomedullin (AM) has two known receptors formed by the calcitonin receptor-like receptor (CL) and receptor activity-modifying protein (RAMP) 2 or 3: we report the effects of the antagonist fragments of human AM and CGRP (AM22-52 and CGRP8-37) in inhibiting AM at human (h), rat (r) and mixed species CL/RAMP2 and CL/...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0705472
更新日期：2003-10-01 00:00:00
abstract：:1. The effects of formoterol, a beta 2-adrenoceptor agonist, on plasma protein exudation and microvascular permeability induced by topical, i.e. applied onto the tracheal mucosal surface, bradykinin (10 nmol; 20 microM, 5 min, 0.1 ml min-1) were studied in a perfused segment of trachea prepared in situ in anaesthetize...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1995.tb16374.x
更新日期：1995-09-01 00:00:00
abstract：BACKGROUND AND PURPOSE:The thiazolidine carboxylic acid, BML-241, has been proposed as a lead compound in development of selective antagonists at the sphingosine-1-phosphate receptor (S1P3), based on its inhibition of the rise in intracellular calcium concentrations ([Ca2+]i) in HeLa cells overexpressing S1P receptors....
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0706872
更新日期：2006-10-01 00:00:00
abstract：:1. The effect of 4-aminopyridine (4-AP) on the slow afterhyperpolarization (sAHP) seen after high frequency dendritic or somatic firing was investigated in rat hippocampal CA1 pyramidal neurones (PC). Intracellular recordings were obtained from the distal apical dendrites and somata and suprathreshold depolarizing cur...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0704533
更新日期：2002-02-01 00:00:00
abstract：:1 Inactivation of prostaglandin E2 in the pulmonary circulation of rabbits in vivo was measured by comparing the hypotensive effects of doses given intravenously and intra-arterially. 2 Di-4-phloretin phosphate (DPP) 25-100 mug kg-1 min-1 inhibited the inactivation of prostaglandin E2 in the pulmonary circulation. 3 T...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1975.tb07569.x
更新日期：1975-07-01 00:00:00
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：BACKGROUND AND PURPOSE:Caffeine is one of the most commonly used psychoactive substances. Circadian rhythms consist of the main suprachiasmatic nucleus (SCN) clocks and peripheral clocks. Although caffeine lengthens circadian rhythms and modifies phase changes in SCN-operated rhythms, the effects on caffeine on the pha...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.12890
更新日期：2014-12-01 00:00:00
abstract：:The effect of baclofen, the GABAB-agent, on the potassium-evoked release of endogenous 5-hydroxytryptamine (5-HT) from slices of mouse frontal cortex has been investigated. The release of endogenous 5-HT evoked by addition of K+ (35 mM) was inhibited by (+/-)-baclofen in a dose-dependent manner with an IC50 of 0.1 mic...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1987.tb11244.x
更新日期：1987-07-01 00:00:00
abstract：BACKGROUND AND PURPOSE:5alpha,8alpha-Epidioxy-22E-ergosta-6, 22-dien-3beta-ol (ergosterol peroxide) is a major antitumour sterol produced by edible or medicinal mushrooms. However, its molecular mechanism of action has yet to be determined. Here, we examine the anticancer and anti-inflammatory effects of ergosterol per...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0706972
更新日期：2007-01-01 00:00:00
abstract：:The sequence similarity within the amino-terminal regions of parathyroid hormone (PTH) and PTH-related protein (PTHrP) allows the two to share actions at a common site, the PTH1 receptor. A number of biological activities have been ascribed to actions of other domains within PTHrP. PTHrP production by late stage breas...
journal_title：British journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1111/bph.14709
更新日期：2019-05-14 00:00:00
abstract：:1. The aim of the present study was to explore the contribution of adrenergic, sensory and nitrergic innervations to the inhibitory effects of the beta2-adrenoceptor agonist clenbuterol on responses to electrical field stimulation (EFS, 200 mA, 0.3 ms, 1-16 Hz, for 30 s, at 1 min interval) in rat mesenteric artery seg...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0701856
更新日期：1998-06-01 00:00:00
abstract：:The smooth muscle relaxant responses to the mixed beta(3)-, putative beta(4)-adrenoceptor agonist, (-)-CGP 12177 in rat colon are partially resistant to blockade by the beta(3)-adrenoceptor antagonist SR59230A suggesting involvement of beta(3)- and putative beta(4)-adrenoceptors. We now investigated the function of th...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0703365
更新日期：2000-06-01 00:00:00
abstract：:The control of ligand-gated receptors with light using photochromic compounds has evolved from the first handcrafted examples to accurate, engineered receptors, whose development is supported by rational design, high-resolution protein structures, comparative pharmacology and molecular biology manipulations. Photoswit...
journal_title：British journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1111/bph.14022
更新日期：2018-06-01 00:00:00
abstract：:The intravenous administration of naloxone 2 min before coronary artery occlusion in anaesthetized dogs reduced the incidence and severity of cardiac arrhythmias during coronary occlusion (20 min) and reperfusion (120 min) in a dose-related manner. It also reduced the mortality. At a dose of 1 mg kg-1 (the maximum dos...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1986.tb10186.x
更新日期：1986-03-01 00:00:00
abstract：:The effect of adenosine on transepithelial ion transport was investigated in isolated preparations of murine trachea mounted in Ussing chambers. The possible regulation of adenosine receptors in an established model of allergic airway inflammation was also investigated. Mucosally applied adenosine caused increases in ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0706133
更新日期：2005-04-01 00:00:00
abstract：:1. Histamine contracted the tracheal and major bronchial muscles of sheep and relaxed the muscles of the lesser bronchi and bronchioles.2. The stimulant action of histamine on the trachea was antagonized by mepyramine, whereas the relaxant effect on the bronchial tree was not.3. 5-Hydroxytryptamine contracted the musc...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1969.tb07997.x
更新日期：1969-07-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Humanized mice for the nuclear receptor peroxisome proliferator-activated receptor δ (PPARδ), termed PPARδ knock-in (PPARδ KI) mice, were generated for the investigation of functional differences between mouse and human PPARδ and as tools for early drug efficacy assessment. EXPERIMENTAL APPROACH...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.2011.01359.x
更新日期：2011-09-01 00:00:00
abstract：BACKGROUND AND PURPOSE:GPR18 is a recently deorphaned lipid receptor that is activated by the endogenous lipid N-arachidonoyl glycine (NAGly) as well the behaviourally inactive atypical cannabinoid, abnormal cannabidiol (Abn-CBD). The presence and/or function of any GPR18-based ocular signalling system remain essential...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.12136
更新日期：2013-06-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Up-regulation of thioredoxin interacting protein (TXNIP), an endogenous inhibitor of thioredoxin (Trx), compromises cellular antioxidant and anti-apoptotic defences and stimulates pro-inflammatory cytokines expression, implying a role for TXNIP in apoptosis. Here we have examined the causal role ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.2011.01336.x
更新日期：2011-09-01 00:00:00
abstract：:1. Some hydroxy-, amino-, and methoxy- phenylalkyltrimethylammonium compounds, beta-pyridylmethyl- dimethylamine and pyrrolidine, and beta-pyridylethyltrimethylammonium, were tested on avoidance learning in mice and their effects were compared with those of (-)-nicotine.2. The o- and m- hydroxybenzyl-, o-hydroxyphenet...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1970.tb10372.x
更新日期：1970-07-01 00:00:00
abstract：BACKGROUND AND PURPOSE:The beneficial effect of 5-HT6 receptor antagonism in cognition remains controversial. This study has been undertaken to reassess the cognition enhancing properties of acute vs subchronic treatment with the selective 5-HT6 receptor antagonist SB-271046 in unimpaired rats, as well as against scopo...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/bjp.2008.281
更新日期：2008-10-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Chemokines and their receptors form an intricate interaction and signalling network that plays critical roles in various physiological and pathological cellular processes. The high promiscuity and apparent redundancy of this network makes probing individual chemokine/receptor interactions and fun...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.14132
更新日期：2018-05-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Activation of cannabinoid receptors decreases emesis, inflammation, gastric acid secretion and intestinal motility. The ability to modulate intestinal permeability in inflammation may be important in therapy aimed at maintaining epithelial barrier integrity. The aim of the present study was to de...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.2011.01589.x
更新日期：2012-04-01 00:00:00
abstract：:Arthritis-associated inflammatory pain represents a serious medical problem worldwide. Current treatments for arthritic pain are not very effective and cause unwanted side effects. Resolvins, including the resolvin D and resolvin E series, are a family of novel endogenous lipid mediators derived from ω-3 polyunsaturat...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.2011.01348.x
更新日期：2011-09-01 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 effects of general anaesthetics on the responses of neurones to iontophoretically applied L-glutamate have been examined in slices of the guinea-pig olfactory cortex in vitro. 2 Concentrations of pentobarbitone, ether, methoxyflurance, trichloroethylene and alphaxalone that are known to depress synaptic transmis...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：
更新日期：1976-11-01 00:00:00
abstract：:1. Optimal dipeptide and peptidomimetic drug transport across the intestinal mucosal surface is dependent upon the co-operative functional activity of the di/tripeptide transporter hPepT1 and the Na(+)/H(+) exchanger NHE3. The ability of the anti-absorptive enteric neuropeptide VIP (vasoactive intestinal peptide) to m...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0705049
更新日期：2003-02-01 00:00:00
abstract：BACKGROUND:Anandamide (AEA) activates both cannabinoid CB(1) and TRPV1 receptors, which are expressed on cultured dorsal root ganglion neurones. Increased levels of nerve growth factor (NGF) are associated with chronic pain states. EXPERIMENTAL APPROACH:The aim of this study was to compare of the effects of AEA on CB(...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0707411
更新日期：2007-10-01 00:00:00
