Abstract:
BACKGROUND AND PURPOSE:While arachidonyl ethanolamine (anandamide) produces pharmacological effects mediated by cannabinoid CB1 receptors, it is also an agonist at the transient receptor potential vanilloid type 1 (TRPV1) ion channel. This study examined the cellular actions of anandamide in the midbrain periaqueductal grey (PAG), a region implicated in the analgesic actions of cannabinoids, and which expresses both CB1 receptors and TRPV1. EXPERIMENTAL APPROACH:In vitro whole cell patch clamp recordings of glutamatergic excitatory postsynaptic currents (EPSCs) were made from rat and mouse PAG slices. KEY RESULTS:Capsaicin (1 µM) increased the rate, but not the amplitude of miniature EPSCs in subpopulations of neurons throughout the rat and mouse PAG. Capsaicin had no effect on miniature EPSCs in PAG neurons from TRPV1 knock-out mice. In mouse PAG neurons, anandamide (30 µM) had no effect on the rate of miniature EPSCs alone, or in the presence of either the CB1 antagonist AM251 (3 µM) or the TRPV1 antagonist iodoresiniferatoxin (300 nM). Anandamide produced a decrease in miniature EPSC rate in the presence of the fatty acid amide hydrolase (FAAH) inhibitor URB597 (1 µM). By contrast, anandamide produced an increase in miniature EPSC rate in the presence of both URB597 and AM251, which was absent in TRPV1 knock-out mice. CONCLUSIONS AND IMPLICATIONS:These results suggest that the actions of anandamide within PAG are limited by enzymatic degradation by FAAH. FAAH blockade unmasks both presynaptic inhibition and excitation of glutamatergic synaptic transmission which are mediated via CB1 receptors and TRPV1 respectively.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Kawahara H,Drew GM,Christie MJ,Vaughan CWdoi
10.1111/j.1476-5381.2010.01157.xsubject
Has Abstractpub_date
2011-07-01 00:00:00pages
1214-22issue
6eissn
0007-1188issn
1476-5381journal_volume
163pub_type
杂志文章abstract::1. The aim of this study was to characterize the tachykinin NK2 receptor subtype mediating the spasmogenic response in the human isolated bronchus. The motor response to neurokinin A (NKA) and the selective NK2 agonist [beta Ala8]NKA(4-10), as well as the antagonistic effects of cyclic (L659,877) and linear (MEN 10376...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1994.tb14775.x
更新日期:1994-02-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Accumulated evidence suggests that oxidative stress is involved in amyloid beta (Abeta)-induced cognitive dysfunction. Silibinin (silybin), a flavonoid derived from the herb milk thistle (Silybum marianum), has been shown to have antioxidative properties; however, it remains unclear whether silib...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2009.00295.x
更新日期:2009-08-01 00:00:00
abstract::Almost all existing models for G-protein-coupled receptors (GPCRs) are based on the occurrence of monomers. Recent studies show that many GPCRs are dimers. Therefore for some receptors dimers and not monomers are the main species interacting with hormones/neurotransmitters/drugs. There are reasons for equivocal interp...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1038/sj.bjp.0707571
更新日期:2008-03-01 00:00:00
abstract::1. We have investigated the effects of the selective phosphodiesterase (PDE) type 4 inhibitor, rolipram (0.01-1 microM) on cytosolic Ca2+ fluxes in FMLP-activated human neutrophils, as well as on superoxide production by, and release of elastase from, these cells. 2. Cytosolic Ca2+ fluxes were measured by use of fura-...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0701849
更新日期:1998-06-01 00:00:00
abstract::1. A study has been made of the effects of cocaine and sympathetic denervation on responses of the cat spleen to (-)-noradrenaline and (-)-isoprenaline.2. Responses of isolated strips of spleen capsule to (-)-noradrenaline or to (-)-isoprenaline were not affected by reserpine-pretreatment.3. In adult cats, cocaine (1 ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1973.tb08255.x
更新日期:1973-08-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Angiotensin AT1 receptor antagonists induce weight loss; however, the mechanism underlying this phenomenon is unknown. The Mas receptor agonist angiotensin-(1-7) is a metabolite of angiotensin I and of angiotensin II . As an agonist of Mas receptors, angiotensin-(1-7) has beneficial cardiovascula...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.13172
更新日期:2015-08-01 00:00:00
abstract::1. The pathological features of Gram-positive shock can be mimicked by the co-administration of two cell wall components of Staphylococcus aureus, namely lipoteichoic acid (LTA) and peptidoglycan (PepG). This is associated with the expression of the inducible isoform of nitric oxide synthase (iNOS) in various organs. ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1996.tb16053.x
更新日期:1996-12-01 00:00:00
abstract::The protease inhibitor ritonavir is an integral part of current antiretroviral therapy targeting human immunodeficiency virus. Recent studies demonstrate that ritonavir induces apoptotic cell death with high efficiency in lymphoblastoid cell lines. Moreover, ritonavir can suppress activation of the transcription facto...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0706023
更新日期:2004-12-01 00:00:00
abstract::1. The role of adenosine 3':5'-cyclic monophosphate (cyclic AMP) in the regulation of catecholamine (CA) secretion in chromaffin cells remains equivocal from previous studies. 2. In the present study the effect of this cyclic nucleotide on basal CA secretion, as well as on intracellular calcium and membrane potential ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1995.tb13257.x
更新日期:1995-01-01 00:00:00
abstract:BACKGROUND AND PURPOSE:We have previously shown that lipid mediators, produced by phospholipase D and C, are generated in OX(1) orexin receptor signalling with high potency, and presumably mediate some of the physiological responses to orexin. In this study, we investigated whether the ubiquitous phospholipase A(2) (PL...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2009.00535.x
更新日期:2010-01-01 00:00:00
abstract::Knowledge of the cardiac safety of emerging new drugs is an important aspect of assuring the expeditious advancement of the best candidates targeted at unmet medical needs while also assuring the safety of clinical trial subjects or patients. Present methodologies for assessing drug-induced torsades de pointes (TdP) a...
journal_title:British journal of pharmacology
pub_type:
doi:10.1038/bjp.2008.279
更新日期:2008-08-01 00:00:00
abstract::Aspirin at therapeutic concentrations does not inhibit the uptake of 5-hydroxytryptamine (5-HT) by blood platelets nor induce release of 5-HT from platelets, although platelet aggregation responses to collagen and arachidonic acid (which are dependent on platelet prostaglandin synthesis) are abolished. This does not s...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1977.tb07735.x
更新日期:1977-04-01 00:00:00
abstract::1. We have investigated the effects of a standardised mixture of hydroxyethylrutosides (HR, Venoruton), a mixture of five of its main components (M) and each of the five components separately (7-mono-HR, 7,4'-di-HR, 7,3',4'-tri-HR, 5,7,3',4'-tetra-HR and 7,3'4'-tri HQ) upon the permeability of single perfused capillar...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1993.tb13792.x
更新日期:1993-09-01 00:00:00
abstract::1. The effect of clofibrate (CFB), bezafibrate (BFB), and gemfibrozil (GFB) on plasma lipoprotein (VLDL and LDL) concentration, composition and resistance to copper-induced oxidation has been studied in male Sprague-Dawley rats after a 15 day treatment. 2. Plasma triglyceride levels were reduced by CFB (41%) and BFB (...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1996.tb16710.x
更新日期:1996-03-01 00:00:00
abstract::1. The rate of gastric emptying was measured directly in 14 convalescent hospital patients and paracetamol absorption was studied following an oral dose of 1.5 g.2. Rapid gastric emptying was associated with the early appearance of high peak plasma paracetamol concentrations whereas peak concentrations were low and oc...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1973.tb08339.x
更新日期:1973-02-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Inhibitors of phosphodiesterase 5 (PDE5) affect signalling pathways by elevating cGMP, which is a second messenger involved in processes of neuroplasticity. In the present study, the effects of the PDE5 inhibitor, sildenafil, on the pathological features of Alzheimer's disease and on memory-relat...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2011.01517.x
更新日期:2011-12-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Here, we have compared the neurochemical profile of three new cathinones, butylone, mephedrone and methylone, in terms of their potential to inhibit plasmalemmal and vesicular monoamine transporters. Their interaction with 5-HT and dopamine receptors and their psychostimulant effect was also stud...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2012.01998.x
更新日期:2012-09-01 00:00:00
abstract::Extracellular nucleotides can activate a common purinoceptor mediating various cell responses. In this study we report that stimulation of rat mesangial cells with ATP and UTP leads to a rapid activation of the protein kinase B/Akt (PKB) pathway. Time-course studies reveal a rapid and transient phosphorylation of both...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0704748
更新日期:2002-06-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Inhibitors of histone deacetylase (HDAC) are emerging as a promising class of anti-cancer drugs, but a generic deregulation of transcription in neoplastic cells cannot fully explain their therapeutic effects. In this study we evaluated alternative molecular mechanisms by which HDAC inhibitors cou...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0707608
更新日期:2008-02-01 00:00:00
abstract::Synaptic transmission in the isolated olfactory cortex slice from the rat was monitored by recording the surface field potentials evoked on lateral olfactory tract (LOT) stimulation. Catechol (approximately 0.05 to 2 mM) caused a concentration-dependent, partially reversible increase in the amplitudes of all field pot...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1986.tb10221.x
更新日期:1986-06-01 00:00:00
abstract::1. The actions on the taenia of 4-(m-chlorophenylcarbamoyloxy)-2-butynyl-trimethylammonium chloride (McN-A-343), N-benzyl-3-pyrrolidyl acetate methobromide (AHR-602), tetramethylammonium (TMA) and choline phenyl ether have been examined and compared with the actions of acetylcholine, nicotine and 1,1-dimethyl-4-phenyl...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1969.tb08303.x
更新日期:1969-05-01 00:00:00
abstract::Perivascular adipose tissue (PVAT) is now recognized as an active player in vascular homeostasis. The expansion of PVAT in obesity and its possible role in vascular dysfunction have attracted much interest. In terms of the regulation of vascular tone and blood pressure, PVAT has been shown to release vasoactive mediat...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1111/bph.13767
更新日期:2017-10-01 00:00:00
abstract:BACKGROUND AND PURPOSE:The two longest C-termini of the purinergic P2X receptors occur in the P2X2 and P2X7 receptors and are thought to interact with multiple cytoplasmic proteins, among which are members of the cytoskeleton, including microtubules. In this work we asked whether disrupting the microtubule cytoskeleton...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2011.01254.x
更新日期:2011-07-01 00:00:00
abstract::1. An investigation was carried out to determine if the sympathoinhibition caused by urapidil is due to activation of 5-HT1A receptors by investigating whether it could be reversed by the non-selective 5-HT1A receptor antagonist spiperone. To control for the possibility of functional antagonism by spiperone, the abili...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1991.tb12290.x
更新日期:1991-04-01 00:00:00
abstract::1. The vascular effects of endothelin and localization of endothelin-like immunoreactivity were characterized in isolated cerebral arteries of dogs. 2. Endothelin-like immunoreactivity was detected in a few populations of endothelial cells of dog basilar artery. 3. Endothelin-1, endothelin-2 and endothelin-3 contracte...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1991.tb12312.x
更新日期:1991-05-01 00:00:00
abstract::1. The involvement of peripheral nitric oxide (NO) in febrigenic signaling to the brain has been proposed because peripherally administered NO synthase (NOS) inhibitors attenuate lipopolysaccharide (LPS)-induced fever in rodents. However, how the unstable molecule of NO can reach the brain to trigger fever is unclear....
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0705713
更新日期:2004-04-01 00:00:00
abstract::The monamine oxidase (MAO) inhibitors harmaline, tranylcypromine, deprenyl, clorgyline and iproniazid were injected intraperitoneally for five days to rabbits at doses that produced significant MAO inhibition. The first three inhibitors raised the concentrations of pyruvate and lactate in blood, decreased the activity...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1985.tb11109.x
更新日期:1985-12-01 00:00:00
abstract:BACKGROUND AND PURPOSE:The P2X(7) receptor exhibits complex pharmacological properties. In this study, binding of a [(3)H]-labelled P2X(7) receptor antagonist to human P2X(7) receptors has been examined to further understand ligand interactions with this receptor. EXPERIMENTAL APPROACH:The P2X(7) receptor antagonist, ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0707196
更新日期:2007-05-01 00:00:00
abstract::The study was undertaken to investigate the 5-HT receptor mediating the inhibitory effect of 5-HT on peristalsis in the guinea-pig isolated ileum. The facilitatory and inhibitory effects were measured as the decrease and increase, respectively, in the intraluminal pressure required to trigger peristalsis. In the prese...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0705184
更新日期:2003-04-01 00:00:00
abstract::1. The aim of the present study was to investigate the role of nitric oxide (NO), histamine and leukotrienes in bronchial obstruction. For this, guinea-pigs immunised against ovalbumin were studied under anaesthesia during challenge with antigen or agonists. 2. Challenge with nebulised antigen (0.1-1 mg) elicited dose...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1995.tb15950.x
更新日期:1995-12-01 00:00:00