Abstract：
BACKGROUND AND PURPOSE:Evidence suggests that phosphorylation of TRPV1 is an important component underlying its aberrant activation in pathological pain states. To date, the detailed pharmacology of diverse TRPV1 receptor agonists and antagonists has yet to be reported for native TRPV1 under phosphorylating conditions. Our goal was to optimize a relatively high-throughput methodology to allow pharmacological characterization of the native TRPV1 receptor using a spinal cord neuropeptide release assay under naive and phosphorylating states. EXPERIMENTAL APPROACH:Herein, we describe characterization of rodent TRPV1 by measurement of CGRP release from acutely isolated lumbar (L1-L6) spinal cord using a 96-well technique that combines use of native, adult tissue with quantitation of CGRP release by ELISA. KEY RESULTS:We have studied a diverse panel of TRPV1 agonists and antagonists under basal and phosphorylating conditions. We show that TRPV1-mediated CGRP release is evoked, in a temperature-dependent manner, by a PKC activator, phorbol 12,13-dibutyrate (PDBu); and that treatment with PDBu increases the potency and efficacy of known TRPV1 chemical agonists, in an agonist-specific manner. We also show that the pharmacological profile of diverse TRPV1 antagonists is dependent on whether the stimulus is PDBu or capsaicin. Of note, HPPB was identified as an antagonist of capsaicin-evoked, but a potentiator of PDBu-evoked, CGRP release. CONCLUSIONS AND IMPLICATIONS:Our findings indicate that both TRPV1 agonist and antagonist profiles can be differentially altered by PKC activation. These findings may offer new insights for targeting TRPV1 in pain states.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Mogg AJ,Mill CE,Folly EA,Beattie RE,Blanco MJ,Beck JP,Broad LMdoi
10.1111/bph.12005subject
Has Abstractpub_date
2013-02-01 00:00:00pages
1015-29issue
4eissn
0007-1188issn
1476-5381journal_volume
168pub_type
杂志文章abstract：:1 The actions and interactions of adenosine and dipyridamole were investigated on isolated strips of coronary arteries of beef cattle. It was found that small diameter arteries (about 0.5-1.0 mm o9d.), raised to a moderate level of tone with potassium, responded with relaxation to low concentrations of adenosine. 2 Di...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1975.tb06949.x
更新日期：1975-11-01 00:00:00
abstract：:The uncoupling activity of oxyclozanide in warm blooded animals has been studied in whole animals, isolated tissue in vitro and on mitochondrial preparations. The onset of post mortem rigidity in mice and rats is accelerated and a contracture of striated muscle is produced. Oxyclozanide (1 muM) stimulated rat liver mi...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1974.tb09622.x
更新日期：1974-03-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Pharmacokinetic/pharmacodynamic (PK/PD) models are necessary to relate the degree of drug exposure in vivo to target blockade and pharmacological efficacy. This manuscript describes a murine agonist-induced CXCR3 receptor internalization assay and demonstrates its utility for PK/PD analyses. EXP...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0707519
更新日期：2007-12-01 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：BACKGROUND AND PURPOSE:Erectile dysfunction is highly prevalent in diabetic patients and PDE V inhibitors are effective and safe for the treatment of erectile dysfunction in men with diabetes. Therefore, in this study we investigated whether a pharmacokinetic interaction occurs between DA-8159 and metformin, as both dr...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0707680
更新日期：2008-04-01 00:00:00
abstract：:Pulmonary fibrosis represents the end stage of a number of heterogeneous conditions and is, to a greater or lesser degree, the hallmark of the interstitial lung diseases. It is characterized by the excessive deposition of extracellular matrix proteins within the pulmonary interstitium leading to the obliteration of fu...
journal_title：British journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1111/j.1476-5381.2011.01247.x
更新日期：2011-05-01 00:00:00
abstract：:Cysteine is one of the two key sulfur-containing amino acids with important functions in redox homeostasis, protein functionality and metabolism. Cysteine is taken up by mammals via their diet and can also be derived from methionine via the transsulfuration pathway. The cellular concentration of cysteine is kept withi...
journal_title：British journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1111/bph.14464
更新日期：2019-02-01 00:00:00
abstract：:1. The purpose of this study was to develop and validate an integrated pharmacokinetic-pharmacodynamic model for the anti-lipolytic effects of the adenosine A1-receptor agonist N6-(p-sulphophenyl)adenosine (SPA). Tissue selectivity of SPA was investigated by quantification of haemodynamic and anti-lipolytic effects in...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0701412
更新日期：1997-10-01 00:00:00
abstract：BACKGROUND AND PURPOSE:An influx drug/proton antiporter of unknown structure has been functionally demonstrated at the blood-brain barrier. This transporter, which handles some psychoactive drugs like diphenhydramine, clonidine, oxycodone, nicotine and cocaine, could represent a new pharmacological target in drug addic...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.13258
更新日期：2015-10-01 00:00:00
abstract：:1. A murine macrophage cell line, J774, expressed nitric oxide (NO) synthase activity in response to interferon-gamma (IFN-gamma, 10 u ml-1) plus lipopolysaccharide (LPS, 10 ng ml-1). The enzyme activity was first detectable 6 h after incubation, peaked at 12 h and became undetectable after 48 h. 2. The decline in the...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1993.tb12886.x
更新日期：1993-03-01 00:00:00
abstract：:1. The aim of the present study was to examine whether ramipril induces delayed myocardial protection against free radical injuries ex vivo and to determine the possible role of the bradykinin B2-nitric oxide (NO) pathway, prostaglandins(PGs) and protein synthesis in this delayed adaptive response. 2. Rats were pretre...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0702089
更新日期：1998-10-01 00:00:00
abstract：:1. Both in mammalian tissues and in transfected cells, only low levels of alpha1D-adrenoceptors are detected in radioligand binding studies. It has been implicated that the comparatively long N-terminal tail of the alpha1D-adrenoceptor is responsible for the inefficient surface expression of the receptor. 2. In the pr...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0706087
更新日期：2005-03-01 00:00:00
abstract：:1. ZENECA ZD7288 (4-(N-ethyl-N-phenylamino)-1,2-dimethyl-6-(methylamino) pyrimidinium chloride, formerly ICI D7288) is a novel sino-atrial node function modulator which selectively slows sinus node rate. Its effects on haemodynamic function have been studied in pentobarbitone anaesthetized dogs, in comparison with zat...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1994.tb17101.x
更新日期：1994-11-01 00:00:00
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 tha...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0706974
更新日期：2007-02-01 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. The modulation of 4-aminopyridine sensitive transient outward potassium current (4-AP I(to)) by neuropeptide Y (NPY) (100 nM) in rat ventricular myocytes was examined using the whole cell voltage-clamp technique. 2. Continuous exposure to NPY (100 nM) for 3 - 6 h significantly increased 4-AP I(to) density. The stim...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0704643
更新日期：2002-04-01 00:00:00
abstract：:1. The effects of 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), an inhibitor of soluble guanylyl cyclase (sGC), were investigated in aortic rings and ventricular cardiomyocytes from rats. The production of cyclic GMP was stimulated by NO.-donors or carbachol. Additionally, the effects of ODQ were studied in cytos...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0702608
更新日期：1999-06-01 00:00:00
abstract：:1. The efflux and influx of tryptophan across the synaptosomal plasma membrane has been studied under a variety of experimental conditions, in order to examine the mechanism by which depolarization enhances the efflux of tryptophan from superfused synaptosomes. 2. Efflux of [3H]-tryptophan from preloaded superfused sy...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1988.tb11440.x
更新日期：1988-02-01 00:00:00
abstract：BACKGROUNDS AND PURPOSE:Lactic acidosis is a fatal adverse effect of metformin, but the risk factor remains unclear. Multidrug and toxin extrusion 1 (MATE1) is expressed in the luminal membrane of the kidney and liver. MATE1 was revealed to be responsible for the tubular and biliary secretion of metformin. Therefore, s...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.2012.01853.x
更新日期：2012-06-01 00:00:00
abstract：BACKGROUND AND PURPOSE:We determined the effects of treatment with LR-90, an inhibitor of advanced glycation end products, on the mechanical properties of the arterial system in streptozotocin (STZ)-induced diabetic Sprague Dawley rats, using aortic impedance analysis, and further investigated the effects of LR-90 on t...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.12656
更新日期：2014-06-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Early soluble epoxide hydrolase inhibitors (sEHIs) such as 12-(3-adamantan-1-yl-ureido)-dodecanoic acid (AUDA) are effective anti-hypertensive and anti-inflammatory agents in various animal models. However, their poor metabolic stability and limited water solubility make them difficult to use pha...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.2008.00009.x
更新日期：2009-01-01 00:00:00
abstract：BACKGROUND AND PURPOSE:The histamine H4 receptor is widely expressed in cells of immune origin and has been shown to play a role in a variety of inflammatory processes mediated by histamine. In this report, we describe the in vitro and in vivo anti-inflammatory properties of a potent histamine H4 receptor antagonist, A...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.2009.00236.x
更新日期：2009-05-01 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：BACKGROUND AND PURPOSE:Abdominal aortic aneurysm (AAA) is a degenerative disease with irreversible and progressive dilation of the artery. But there are few options for efficacious treatment except for traditional surgery. Probucol has been widely applied to treat hyperlipidaemia and atherosclerosis in clinic, but whet...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.14857
更新日期：2020-01-01 00:00:00
abstract：BACKGROUND AND PURPOSE:The rat respiratory muscle diaphragm has markedly lower sensitivity than the locomotor muscle extensor digitorum longus (EDL) to the new acetylcholinesterase (AChE) inhibitors, alkylammonium derivatives of 6-methyluracil (ADEMS). This study evaluated several possible reasons for differing sensiti...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.2011.01211.x
更新日期：2011-06-01 00:00:00
abstract：:1 Groups of mice were pretreated with the 5-hydroxytryptamine (5-HT) depletors, fenfluramine or p-chlorophenylalanine (PCPA), followed by pethidine or morphine. 2 Fenfluramine alone produced a short lasting analgesia but PCPA was without any effect. 3 Pethidine and morphine both increased hot plate reaction times meas...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1982.tb09177.x
更新日期：1982-04-01 00:00:00
abstract：:1. Platelet-activating factor (PAF), an inflammatory mediator, plays an important role in mediating intestinal injury. However, it remains unclear whether PAF has a function in the intestine. The production of PAF by normal intestine and by unstimulated intestinal epithelial cell lines suggests that PAF may have a reg...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0702939
更新日期：2000-04-01 00:00:00
abstract：:1 The binding of [3H]-5-hydroxytryptamine ([3H]-5-HT), [3H]-haloperidol and [3H]-dopamine to human blood platelets was investigated and the effects of unlabelled haloperidol on [3H]-5-HT binding and (+)- and (-)-butaclamol on [3H]-haloperidol were studied. 2 Scatchard analysis did not show any specific binding of [3H]...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1978.tb07812.x
更新日期：1978-07-01 00:00:00
abstract：:1. The effect of adenosine triphosphate (ATP) and its stable analogues, alpha, beta-methylene-ATP and beta, gamma-methylene-ATP, on the efferent function of capsaicin-sensitive non-adrenergic, non-cholinergic (NANC) nerves was tested in guinea-pig isolated atria. 2. Transmural nerve stimulation of atria isolated from ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1992.tb09011.x
更新日期：1992-03-01 00:00:00
abstract：:The histamine H3 receptor, first described in 1983 as a histamine autoreceptor and later shown to also function as a heteroreceptor that regulates the release of other neurotransmitters, has been the focus of research by numerous laboratories as it represents an attractive drug target for a number of indications inclu...
journal_title：British journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1038/bjp.2008.147
更新日期：2008-07-01 00:00:00
