Abstract:
INTRODUCTION:Challenge of guinea-pig tracheal epithelium with hyperosmolar solution alters ion transport and evokes the release of epithelium-derived relaxing factor (EpDRF). Cultured tracheal epithelial cells (CE) offer the potential to examine biochemical pathways related to EpDRF release, but whether the bioelectric properties and responses of fresh, adherent epithelial cells (FE) are modeled by CE has not been established. METHODS:Tracheal epithelial cells grown in air-interface culture and fresh tracheal segments were mounted in Ussing chambers to determine short circuit current (I(sc)) and transepithelial resistance (R(t)) and to compare responses to transport inhibitors, methacholine and hyperosmolarity. RESULTS:Significant differences in basal I(sc) and R(t) between FE and CE were observed (I(sc), 41.3+/-3.5 and 8.5+/-0.8 microA/cm(2), P<0.05; R(t), 106+/-7 and 422+/-4 Omega cm(2), P<0.05; respectively); basal spontaneous potential difference values were not different (4.2+/-0.3 and 3.4+/-0.3 mV, respectively). Amiloride (mucosal, 3 x 10(-5) M), bumetanide (basolateral, 10(-5) M) and ouabain (basolateral, 10(-5) M) reduced I(sc) equally in FE and CE. In contrast, NPPB (10(-5) M) in the presence of amiloride had a differential effect, decreasing I(sc) by 11% in FE and 71% in CE (P<0.05). Iberiotoxin (basolateral, 10(-7) M) was without effect in either preparation. In FE, serosal methacholine (3x10(-5) M) elicited an NPPB-insensitive monotonic increase in I(sc), but in CE caused a large, transient, NPPB-inhibitable increase which was followed by an NPPB-resistant plateau. Addition of apical D-mannitol (0.3-267 mosM) to increase osmolarity decreased I(sc) in FE, whereas in CE d-mannitol initially increased (0.3-84.3 mosM) and then decreased (84.3-267 mosM) I(sc). DISCUSSION:Cell culture causes substantial changes in the bioelectric and pharmacological properties of respiratory epithelium. Caution should be exercised when using CE as a substitute for FE in studies of ion transport- and cell volume-dependent processes.
journal_name
J Pharmacol Toxicol Methodsjournal_title
Journal of pharmacological and toxicological methodsauthors
Fedan JS,Wu DX,Van Scott MRdoi
10.1016/j.vascn.2006.04.005subject
Has Abstractpub_date
2007-03-01 00:00:00pages
135-43issue
2eissn
1056-8719issn
1873-488Xpii
S1056-8719(06)00057-8journal_volume
55pub_type
杂志文章abstract::This editorial prefaces the annual themed issue on safety pharmacology (SP) methods published in the Journal of Pharmacological and Toxicological Methods (JPTM). We highlight here the content derived from the recent 2016 Safety Pharmacology Society (SPS), Canadian Society of Pharmacology and Therapeutics (CSPT), and J...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 社论
doi:10.1016/j.vascn.2017.04.012
更新日期:2017-09-01 00:00:00
abstract::The relative importance of the discipline of safety pharmacology (which integrates physiology, pharmacologyand toxicology) has evolved since the incorporation of the Safety Pharmacology Society (SPS) as an entity on August 10, 2000. Safety pharmacology (SP), as a synthesis of these other fields of knowledge, is concer...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 社论
doi:10.1016/j.vascn.2015.05.013
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abstract::The use of animal models is an essential part of medical research and drug development. The essential skills required to be able to do such research includes experimental design, statistical analysis and the actual handling and treating of the animals (in vivo skills). The number of students in the U.K. receiving trai...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/j.vascn.2011.07.002
更新日期:2011-09-01 00:00:00
abstract:INTRODUCTION:Excitation of Acetylcholine-mediated (Ach) transmission (especially if irreversible) may pose life-threatening adverse events by increasing neuronal network activity. Unfortunately, adequate detection of this liability during early drug development is hampered, because published ex vivo electrophysiologica...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/j.vascn.2014.12.001
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abstract:INTRODUCTION:Parts A and B of the ICH S7 guidelines on safety pharmacology describe the in vivo studies that must be conducted prior to first time in man administration of any new pharmaceutical. ICH S7A requires a consideration of the sensitivity and reproducibility of the test systems used. This could encompass maint...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章,多中心研究
doi:10.1016/j.vascn.2013.04.008
更新日期:2013-07-01 00:00:00
abstract:INTRODUCTION:The ICH S7B guidelines recommend that all new chemical entities should be subjected to hERG repolarization screening due to its association with life-threatening "Torsades de Pointes" (TdP) arrhythmia. However, it has become evident that not all hERG channel inhibitors result in TdP and not all compounds t...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/j.vascn.2016.06.004
更新日期:2016-09-01 00:00:00
abstract:INTRODUCTION:The cytochrome P450 CYP26 family of retinoic acid (RA) metabolizing enzymes, comprising CYP26A1, CYP26B1, and CYP26C1 is critical for establishing patterns of RA distribution during embryonic development and retinoid homeostasis in the adult. All three members of this family can metabolize all trans-RA. CY...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/j.vascn.2011.08.005
更新日期:2011-11-01 00:00:00
abstract::Buffers used to incubate cells for pharmacological or toxicological studies are usually of very simple composition, far from the composition of biological fluids or cell culture media. Comparative studies on taurine uptake levels by cultured cells show that a new CO2-Independent Medium (CIM) is suitable for incubating...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/s1056-8719(98)00020-3
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abstract::The objective of this research is to determine whether the administration of a complete soft food formula to sub-lethal irradiated animals from three different transgenic mouse strains over a period of 21 consecutive days will have a significant impact on the clinical signs, and the general survival rate of the animal...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/j.vascn.2014.12.003
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journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/1056-8719(94)90008-6
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journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/j.vascn.2010.04.004
更新日期:2010-07-01 00:00:00
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journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/s1056-8719(98)00044-6
更新日期:1998-10-01 00:00:00
abstract::The acetylcholine-evoked relaxation of rabbit isolated thoracic aorta precontracted by phenylephrine was studied. Phenylephrine caused a steady contraction that was maintained for 6 h. In the presence of calcium disodium ethylenediaminetetraacetate (EDTA) and ascorbic acid the contraction decreased with time. N(G)-Nit...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/s1056-8719(99)00035-0
更新日期:1999-08-01 00:00:00
abstract:INTRODUCTION:The analytical solutions to compartmental pharmacokinetic models are well known, but have not been presented in a form that easily allows for complex dosing regimen and changes in covariate/parameter values that may occur at discrete times within and/or between dosing intervals. METHODS:Laplace transforms...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/j.vascn.2015.03.004
更新日期:2015-05-01 00:00:00
abstract:INTRODUCTION:The Health and Environmental Sciences Institute of the International Life Sciences Institute (ILSI/HESI) Cardiovascular Safety Subcommittee outlined a set of in vivo telemetry studies to determine how well this preclinical model identified compounds known to cause torsades de pointes (TdP) and prolong QT i...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/j.vascn.2007.04.002
更新日期:2007-09-01 00:00:00
abstract:INTRODUCTION:Regulatory guidelines recommend the use of conscious, unrestrained animals for comprehensive cardiovascular safety assessment of a new therapeutic agent. Cardiovascular safety pharmacology studies normally use internal telemetry (surgical implants) in free-moving animals to monitor key ECG endpoints, like ...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/j.vascn.2009.04.196
更新日期:2009-07-01 00:00:00
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journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/j.vascn.2013.07.001
更新日期:2013-11-01 00:00:00
abstract:INTRODUCTION:The quantification of [(3)H]noradrenaline spillover from electrically stimulated, sympathetic nerves is a widely used method to study presynaptic effects of hormones, transmitters and drugs. Although a straightforward approach, the execution of the experiments is not trivial. This holds true mainly for a r...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
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abstract:INTRODUCTION:Laboratory investigations into cholestatic liver disease and the effects of cholemia on organ function are long-standing subjects of scientific enquiry. A widely-used strategy to investigate these topics relies on animal-based research using experimental animal models. Targeted inactivation of the spgp gen...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/j.vascn.2004.06.002
更新日期:2004-11-01 00:00:00
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journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/s1056-8719(97)00012-9
更新日期:1997-03-01 00:00:00
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journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/j.vascn.2005.02.004
更新日期:2006-03-01 00:00:00
abstract:INTRODUCTION:In experimental pain research the effect of opioids is normally assessed by verbal subjective response to analgesia. However, as many confounders in pain assessment exist, objective bed-side assessment of the effect is highly warranted. Therefore, we aimed to assess the effect of morphine on three objectiv...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.vascn.2015.01.005
更新日期:2015-05-01 00:00:00
abstract:INTRODUCTION:In vivo profiles of aldosterone synthase inhibitors (ASIs) have been investigated utilizing various rodent models. Due to lack of CYP17 activity, rodents produce corticosterone rather than cortisol as that of humans, which raised concern to their effectiveness in translational pharmacological characterizat...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/j.vascn.2014.09.011
更新日期:2015-01-01 00:00:00
abstract::In many circumstances, rapid information is required about the effects of drugs on neurotransmitter release in brain, and a common method used is measurement of radiolabelled release from superfused brain slices or synaptosomes in vitro. However, the method requires expensive equipment and is not readily adapted to th...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/s1056-8719(97)00010-5
更新日期:1997-04-01 00:00:00
abstract:INTRODUCTION:Multiple cardiac ion channels are prone to block by pharmaceutical compounds, and this can have large implications for cardiac safety. The effect of a compound on individual ion currents can now be measured in automated patch clamp screening assays. In-silico action potential models are proposed as one way...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/j.vascn.2015.05.002
更新日期:2015-09-01 00:00:00
abstract:INTRODUCTION:Gastrointestinal (GI) motility disorders include many clinical manifestations associated with various pathologies. They are widespread and can be considered a primary symptom or can be associated to other diseases, such as Parkinson's disease. Understanding the type and site of GI dysmotility is crucial to...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/j.vascn.2014.08.003
更新日期:2014-09-01 00:00:00
abstract::A method for determination of cis-diaminedichloroplatinum (II) (cisplatin) in ultrafiltered plasma, cell, and tumour samples is described. Cisplatin separation was carried out on a reversed-phase column using methanol-acetonitrile-water as the mobile phase. The flow rate was maintained constant at 1.6 mL/min and analy...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/j.vascn.2005.06.005
更新日期:2005-11-01 00:00:00
abstract:INTRODUCTION:Methods to determine infarct size following ischemia-reperfusion injury include gross staining with triphenyltetrazolium chloride (TTC) and perfusion of colored dyes to demarcate the non-ischemic zone. Infarcted tissue (INF) can typically appear a mottled tan to brownish color, making a border between INF ...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/j.vascn.2006.06.005
更新日期:2007-03-01 00:00:00
abstract::A model of gingival inflammation was performed in Sprague-Dawley rats weighing 180-200 g. Mechanical bamboo stick-induced injury was inflammatory when bacteria contaminated the sticks. Bacteria were first obtained from gingival fluid collected from a patient with adult periodontitis. Another strain from Institut Paste...
journal_title:Journal of pharmacological and toxicological methods
pub_type: 杂志文章
doi:10.1016/1056-8719(94)90070-1
更新日期:1994-11-01 00:00:00